CN102702245A

CN102702245A - Hydrophobic mesoporous nanomaterial and preparation method and application thereof

Info

Publication number: CN102702245A
Application number: CN2012102043341A
Authority: CN
Inventors: 祝迎春; 赵阳
Original assignee: Shanghai Institute of Ceramics of CAS
Current assignee: Jiangsu Institute Of Advanced Inorganic Materials
Priority date: 2012-06-20
Filing date: 2012-06-20
Publication date: 2012-10-03
Anticipated expiration: 2032-06-20
Also published as: CN102702245B

Abstract

The invention discloses a kind of Hydrophobic Mesoporous nano materials and its preparation method and application, the Hydrophobic Mesoporous nano material is to be carried out condensation reaction by ordered mesoporous material and couplingization reagent and obtained, any one of the couplingization reagent in following general formula: Cl-SiR3 or RO-SiR3, R group therein include hydrophobic organic groups. The Hydrophobic Mesoporous nano material is introduced into low-intensity ultrasonic system, low-intensity ultrasonic cavitation effect intensity can be enhanced. Show through inside and outside experiment: hydrophobic nano mesoporous material provided by the invention and low-intensity ultrasonic have apparent synergistic effect, have good cell compatibility and lower cytotoxicity; Especially after solubilising, it is combined with low-intensity ultrasonic, can obviously inhibits tumour growth, have broad application prospects.

Description

A kind of hydrophobicity meso-porous nano material

Technical field

The present invention relates to a kind of meso-porous nano material, specifically, relate to a kind of hydrophobicity meso-porous nano material that can be used for strengthening low-intensity ultrasonic cavitation effect intensity, belong to technical field of function materials.

Background technology

The sickness rate of tumour is increasingly high at present, and tumour is seriously threatening people's life quality and life, and malignant tumour has become the healthy No.1 killer of harm humans in this century.Mainly comprise excision, chemotherapy and radiotherapy to tumor treatment; But all there is obvious toxic and side effects in three kinds of treat-ment, all can not become a kind of effective means of effecting a radical cure tumour separately.Therefore, seek a kind of treatment means safe, effective, quick, that toxic side effect is little and become the new problem in the oncotherapy research.

Ultrasound treatment more and more receives the concern of medical circle as a kind of oncotherapy scheme of non-intrusion type.Ultrasound treatment is historical at the existing last 100 years of the application of treatment tumour.In recent years the supersonic biology Study on Effect is shown that low frequency ultrasound section is as a kind of potential means of treating tumour, cell death inducing is that the important biomolecule of ultrasound treatment malignant tumour is learned one of mechanism.Low frequency ultrasound is decayed low in tissue, compares with the high frequency ultrasound under the equal SPL, and low frequency ultrasound gets into tissue in tissue the degree of depth is bigger, and low frequency low intensity ultrasound heat effect that tissue is caused a little less than.There are some researches show that normal cell has good resistibility to the biological effect of low frequency ultrasound, malignant tumour is then more responsive.Therefore, if can realize adopting low frequency ultrasound to realize effective oncotherapy, then can avoid heating to treat some unfavorable factors of being brought based on high strength supersonic traditionally.Simultaneously, to nano material biological effect and toxicologic research invention thereof, the part nano material can cause cyto-architectural change, produces the toxicity of pair cell, thus cell death inducing.Also have document to disclose low intensity ultrasound and can strengthen ADR, the AZQ CDCC to CHO, MCF-7WT cell, this possibly be ultrasonic making due to aggregate amount increases in the cell for a document analysis.The ultrasonic medicine entering cell tissue that also can be used for making in the particulate.

Research has extensively and profoundly also been carried out in nano material and the application of device in oncotherapy at present.Inorganic nanometer-sized mesoporous structured material (like mesoporous silicon oxide etc.) since its have the pore passage structure of homogeneous, big pore volume and specific surface area, surface is easy to excellent performance such as chemical modification and excellent biological compatibility, fix in the absorption that biological field is widely used in bioactive enzyme, the transmission release of biocatalysis, biosensor, DNA and medicine controlled releasing etc.Document is arranged, and (scientific and technological Leader 2008,26 (22) P66-70) discloses the employing carbon nanotube and can strengthen low frequency low intensity ultrasound inducing apoptosis of tumour cell effect, might become a kind of effective means of oncotherapy.But its concrete mechanism of action does not obtain complete understanding as yet, confirms that nanoparticle type, granule density, ultrasonication time, intensity, frequency etc. are applicable to that also there is certain difficulty in the parameter of treatment.

Summary of the invention

To the problems referred to above that prior art exists, the purpose of this invention is to provide a kind of hydrophobicity meso-porous nano material that can be used for strengthening low-intensity ultrasonic cavitation effect intensity, realize the effective treatment of low-intensity ultrasonic to tumour.

For realizing the foregoing invention purpose, the technical scheme that the present invention adopts is following:

A kind of hydrophobicity meso-porous nano material contains ordered mesoporous material and the coupling reagent react of hydroxyl by the surface and gets, and described coupling reagent is selected from any one in the following general formula: Cl-SiR _{3 or}RO-SiR ₃, R group wherein includes the hydrophobicity organic group.

As a kind of preferred version, described R group includes any one or a few in the hydrophobicity organic groups such as being selected from alkyl, alkylene, alkynes base, fluoroalkyl, phenyl, for example:

As further preferred version; Described coupling reagent is hexamethyldisilazane, tetramethyl-disilazane, 1; 3-divinyl-1; 1,3,3-tetramethyl-disilazane, trimethylchlorosilane, chlorotriethyl silane, ten trifluoro octyl group Trimethoxy silanes, trifluoro propyl triethoxyl silane or 17 fluorine decyl Trimethoxy silanes.

As a kind of preferred version, the channel diameter of described ordered mesoporous material is that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m ²/ g.

As further preferred version, described ordered mesoporous material is ordered mesoporous materials such as MCM-41, MCM-48, SBA-15, MSU, spherical mesoporous Win 40350 or layered mesoporous Win 40350.

A kind of described hydrophobicity meso-porous nano preparation methods comprises the steps: under anhydrous condition, to make ordered mesoporous material and coupling reagent to carry out condensation reaction.

As a kind of preferred version, the operation of said condensation reaction is following: ordered mesoporous material is fully disperseed with organic solvent, add coupling reagent then, under anhydrous condition, in 0～100 ℃ of stirring reaction 2～48 hours; Finish reaction, use organic solvent washing, drying; The mol ratio of ordered mesoporous material and coupling reagent is 1: (0.005～1).

As further preferred version, the operation of said condensation reaction is following: ordered mesoporous material is fully disperseed with normal hexane, add coupling reagent then, under anhydrous condition, in 20～80 ℃ of stirring reactions 6～48 hours; Finish reaction, wash successively with normal hexane, ethanol, in 30～200 ℃ of dryings; The mol ratio of ordered mesoporous material and coupling reagent is 1: (0.01～0.1).

As further preferred version, it is that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m that described ordered mesoporous material is selected from channel diameter ²Any one ordered mesoporous material in the MCM-41 of/g, MCM-48, SBA-15, MSU, spherical mesoporous Win 40350, the layered mesoporous Win 40350; Described coupling reagent is selected from hexamethyldisilazane, tetramethyl-disilazane, 1; 3-divinyl-1; 1; 3, any one in 3-tetramethyl-disilazane, trimethylchlorosilane, chlorotriethyl silane, ten trifluoro octyl group Trimethoxy silanes, trifluoro propyl triethoxyl silane, the 17 fluorine decyl Trimethoxy silanes.

As preferred version further, described ordered mesoporous material is by hydrothermal method or template preparation and get.

A kind of application of described hydrophobicity meso-porous nano material is that described hydrophobicity meso-porous nano material is incorporated in the low-intensity ultrasonic system, to strengthen low-intensity ultrasonic cavitation effect intensity; The frequency of described low-intensity ultrasonic is 0.1～50MHz, and intensity is 0.2～1000W/cm ²

As a kind of preferred version, at first adopt the described hydrophobicity meso-porous nano of solubilizing agent solubilising material, be incorporated into then in the low-intensity ultrasonic system.

As further preferred version, adopt the operation of the described hydrophobicity meso-porous nano of solubilizing agent solubilising material following: hydrophobicity meso-porous nano material and solubilizing agent to be added in the entry, stir 2～48h, use water washing then, drying at 0～100 ℃; The mass ratio of hydrophobicity meso-porous nano material and solubilizing agent is 1: (0.2～5).

As further preferred version; Described solubilizing agent is selected from tween-80, Lip river and moors husky nurse 188, Yelkin TTS, hydroxypropyl-beta-cyclodextrin, hydroxyethyl-, alpha-cylodextrin, γ-Huan Hujing, sulfobutyl ether-beta-cyclodextrin, SANMALT-S-beta-cyclodextrin, 2; 3, any one in 6-fourth sulfo group sodium-beta-cyclodextrin, hydroxypropyl-alpha-cylodextrin, the hydroxypropyl-γ-Huan Hujing.

Compared with prior art, the present invention has following beneficial effect:

Hydrophobicity meso-porous nano material preparation method provided by the invention is simple, and raw material is cheap and easy to get, and reaction conditions is gentle and easy to control the quality; And hydrophobicity meso-porous nano material and low-intensity ultrasonic through after the solubilising processing have the obvious synergistic effect, can significantly strengthen low-intensity ultrasonic cavitation effect intensity; In addition; Hydrophobicity meso-porous nano material provided by the invention has good cell consistency and lower cytotoxicity; And behind solubilising, treat tumour with the low-intensity ultrasonic coupling; In vivo with in the experiment in vitro effect of obvious suppression tumor growth is arranged all, have significant meliority, for oncotherapy provides a kind of new effective means; Therefore its application prospect is very wide, has great social value and meaning.

Description of drawings

The infrared spectrum of the hydrophobicity meso-porous nano material that Fig. 1 provides for embodiment 1;

The TG-DSC of hydrophobicity meso-porous nano material figure behind the solubilising that Fig. 2 provides for embodiment 1;

Hydrophobicity meso-porous nano material is to the fluoroscopic examination spectrogram of ultrasonic cavitation effects behind the solubilising that Fig. 3 provides for embodiment 1;

Hydrophobicity meso-porous nano material lethal effect to cancer cell in vitro under low intensity ultrasound is verified figure as a result behind the solubilising that Fig. 4 provides for embodiment 1;

The intravital anticarcinogenic effect proof diagram of the animal of hydrophobicity meso-porous nano material under low intensity ultrasound behind the solubilising that Fig. 5 provides for embodiment 1;

The graph of pore diameter distribution of the hydrophobicity meso-porous nano material that Fig. 6 provides for embodiment 2;

The BET test pattern of the hydrophobicity meso-porous nano material that Fig. 7 provides for embodiment 2;

The TEM figure of the hydrophobicity meso-porous nano material that Fig. 8 provides for embodiment 2;

Hydrophobicity meso-porous nano material is to the fluoroscopic examination spectrogram of ultrasonic cavitation effects behind the solubilising that Fig. 9 provides for embodiment 4;

The TG-DSC of hydrophobicity meso-porous nano material figure behind the solubilising that Figure 10 provides for embodiment 14;

Hydrophobicity meso-porous nano material lethal effect to cancer cell in vitro under low intensity ultrasound is verified figure as a result behind the solubilising that Figure 11 provides for embodiment 14;

The TG-DSC of hydrophobicity meso-porous nano material figure behind the solubilising that Figure 12 provides for embodiment 25;

Hydrophobicity meso-porous nano material is to the fluoroscopic examination spectrogram of ultrasonic cavitation effects behind the solubilising that Figure 13 provides for embodiment 25;

The MCM-41 mesoporous material that Figure 14 provides for Comparative Examples 1 is to the fluoroscopic examination spectrogram of ultrasonic cavitation effects;

The MCM-41 mesoporous material that Figure 15 provides for Comparative Examples 1 lethal effect to cancer cell in vitro under low intensity ultrasound is verified figure as a result;

Figure 16 is the fluoroscopic examination spectrogram of Comparative Examples 5 when nano material (no) to the ultrasonic cavitation effects.

Embodiment

Below in conjunction with embodiment and Comparative Examples and accompanying drawing to the present invention do further in detail, intactly explanation.Following embodiment:

Utilize x-ray diffractometer (XRD), transmission electron microscope (TEM), infrared (IR), contact angle is measured and thermogravimetric analysis (TG-DSC) is carried out structural characterization to resulting nano material;

Utilize fluorescence spectrum that the generation and the intensity of cavitation effect under the low intensity ultrasound effect are verified, exciting light is 310nm, and solution is terephthaldehyde's acid solution of 5mmol/L, and sample solution concentration is 1mg/mL, ultrasonic 2min;

Utilize laser confocal microscope that tumour cell is verified the performance of engulfing of nano material, hydrophobicity meso-porous nano material behind the solubilising is carried out the FITC fluorescent mark, nucleus carries out the DAPI fluorescent mark;

Hydrophobicity meso-porous nano material synergy is carried out external checking to the result of treatment of ZR75-30 breast cancer cell down after utilizing the MTT detection method to low intensity ultrasound and solubilising;

Hydrophobicity meso-porous nano material is verified the cytotoxicity of ZR75-30 breast cancer cell after utilizing the MTT detection method to solubilising;

Be utilized in and set up tumor model on the nude mouse, it is carried out ultrasound treatment, and carry out pathological section research and verify intravital result of treatment.

The operation of carrying out the cell in vitro experiment is following:

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL; 1mL) transfer to 96 well culture plates; (RPMI1640+10% foetal calf serum) cultivated 24h in substratum, inhales then and abandons nutrient solution, uses that the nutrient solution of hydrophobicity meso-porous nano material continues to cultivate 12h behind the solubilising that contains 0～200 μ g/mL instead; Then use frequency to be 1KHz～50MHz, intensity is 0.2～1000W/cm ² Ultrasonic irradiation 0～20min, use mtt assay to detect cell survival rate after continue cultivating 24h.

The operation of carrying out interior animal experiment is following:

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln of hydrophobicity meso-porous nano material behind the solubilising contain 0～200 μ g/mL, and after injecting 30min, use frequency to be 1KHz～50MHz, intensity is 0.2～1000W/cm ²UW across water bag property irradiation 0～20min at interval, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Used ordered mesoporous material MCM-41, MCM-48, SBA-15, MSU, spherical mesoporous Win 40350 and layered mesoporous Win 40350 all is to adopt Hydrothermal Preparation and get among the embodiment, and it is following specifically to prepare process:

1) preparation of ordered mesoporous material MCM-41

In the NaOH of the 0.1～10mol/L aqueous solution, add cetyl trimethylammonium bromide (CTAB), stir to clarify in 0～100 ℃; Add TEOS, stir; Carried out hydro-thermal reaction 1～48 hour in 25～200 ℃; The material molar ratio that adds is: SiO ₂: NaOH:CTAB:H ₂O=1: (0.1～0.8): (0.1～0.6): (20～80); Taking-up, filtration, washing, drying get crude product PMCM; PMCM places ethanol with crude product, adds the hydrochloric acid of 1mol/L again, and the volume ratio of ethanol and hydrochloric acid is 100:1～10:1; After the reflux 1～24 hour, filter, wash, dry, promptly getting channel diameter is that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m ²The MCM-41 ordered mesoporous material of/g.

2) preparation of ordered mesoporous material MCM-48

In the NaOH of the 0.1～10mol/L aqueous solution, add cetyl trimethylammonium bromide (CTAB), be stirred to dissolving fully in 0～100 ℃; Drip silicon sol (SiO ₂), high degree of agitation 5～60 minutes; Carried out hydro-thermal reaction 1～48 hour in 25～200 ℃; The material molar ratio that adds is: SiO ₂: CTAB:H ₂O:NaOH=1: (0.1～0.8): (0.1～0.6): (20～80); Filtration, washing, drying get the former powder of MCM-48; The former powder of MCM-48 was calcined 2～24 hours down in 150～500 ℃, and promptly getting channel diameter is that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m ²The MCM-48 ordered mesoporous material of/g.

3) preparation of ordered mesoporous material SBA-15

Segmented copolymer P123 is dissolved in the aqueous hydrochloric acid of 0.1～2mol/L, after 0～100 ℃ of stirring and dissolving, adds tetraethoxy (TEOS), continue to stir after 1～48 hour, carried out hydro-thermal reaction 1～48 hour in 25～200 ℃; The material molar ratio that adds is: TEOS:P123:HCl:H ₂O=1: (0.1～0.6): (0.2～2): (10～30); Take out, filter, wash, calcined 2～24 hours down in 150～500 ℃, promptly getting channel diameter is that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m ²The SBA-15 ordered mesoporous material of/g.

4) preparation of ordered mesoporous material MSU

Take by weighing C ₁₈EO ₁₀, heated and stirred is dissolved in the deionized water it fully, and compound concentration is the settled solution of 0.01～1mol/L; PH value to 1～4 of regulator solution after 1～24 hour, add silicon source (tetraethoxy or water glass) in 0～100 ℃ of stirring, carry out hydro-thermal reaction 1～48 hour in 25～200 ℃; The material molar ratio that adds is: TEOS:C ₁₈EO ₁₀=1: (2～20); Filter, wash, at N ₂Protection is down in 150～500 ℃ of roastings 2～24 hours, and promptly getting channel diameter is that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m ²The MSU ordered mesoporous material of/g.

5) preparation of the spherical mesoporous Win 40350 of ordered mesoporous material

Preparation contains the immobilized liquid membrane (SLM) of phenanthroline carrier; With 0.2mol/L CaCl ₂Solution, 0.05mol/L Na ₂HPO ₄Solution joins the SLM left and right sides respectively, and control Ca/P mol ratio is 1～5; At Na ₂HPO ₄Solution one side adds nitrilotriacetic acid(NTA), regulates pH to 7.5～9, carries out hydro-thermal reaction 1～48 hour in 25～200 ℃; With Na ₂HPO ₄The product spinning of solution one side; Water, acetone, absolute ethanol washing successively; Vacuum-drying, promptly getting channel diameter is that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m ²The spherical mesoporous Win 40350 ordered mesoporous material of/g.

6) preparation of the layered mesoporous Win 40350 of ordered mesoporous material

At first compound concentration is that the calcium nitrate aqueous solution of 2～10mol/L, the aqueous ethanolic solution and the concentration of 1-isobutyl-3,5-dimethylhexylphosphoric acid (MDP) that concentration is 1～10mol/L are the ammonium dibasic phosphate aqueous solution of 3～10mol/L; MDP aqueous ethanolic solution refluxing and stirring was added calcium nitrate aqueous solution after 0.5～3 hour, continue stirring and splash into ammonium dibasic phosphate aqueous solution after 0.5～3 hour; Control Ca/P mol ratio is 1: (0.1～5); Regulate pH value to 9, carried out hydro-thermal reaction 1～48 hour in 25～200 ℃; Spinning, washing, drying, in 150～500 ℃ of calcinings 1～24 hour, promptly getting channel diameter was that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m again ²The layered mesoporous Win 40350 ordered mesoporous material of/g.

The preparation of above-mentioned ordered mesoporous material MCM-41, MCM-48, SBA-15, MSU, spherical mesoporous Win 40350 and layered mesoporous Win 40350 all is not limited to hydrothermal method, all can adopt other method preparation of reporting in the prior art and gets.

Embodiment 1

With channel diameter is that 2nm, particle diameter are that 20nm, specific surface area are 1000m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds hexamethyldisilazane then, stirs 24h in 25 ℃; The mol ratio of ordered mesoporous material MCM-41 and hexamethyldisilazane is 1:0.05; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Can find out by Fig. 1 at 2962cm ^-1The existence of the c h bond vibration peak at place explains that methyl is grafted among the ordered mesoporous material MCM-41 through silane coupledization.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:0.3, stir 24h in 25 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Can draw by Fig. 2, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 9.68%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 42%.

Through the laser confocal microscope checking, hydrophobicity meso-porous nano material can normally be engulfed by tumour cell behind the described solubilising, does not cause the death of cell.

In the cytotoxicity of MTT detection method checking FHMSN to the ZR75-30 breast cancer cell, the survival rate of cell explains that more than 95% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Fluorescence spectrum by Fig. 3 can be found out, is 1MHz in frequency, and intensity is 0.2W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 14 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 50 μ g/mL instead and continue to cultivate 12h, then use frequency to be 1MHz, intensity is 0.2W/cm ²Ultrasonic irradiation 8min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 4.7% (seeing shown in Figure 4).

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 50 μ g/mL, and after injecting 30min, use frequency to be 1MHz, intensity is 0.2W/cm ²UW property is according to 5min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

B curve by among Fig. 5 can learn that after treatment, growth of tumor speed has had remarkable decline, and the tumor propagation rate is 41.75% relatively.

Embodiment 2

With channel diameter is that 10nm, particle diameter are that 200nm, specific surface area are 100m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds 1 then, 3-divinyl-1,1,3, and the 3-tetramethyl-disilazane stirs 12h in 60 ℃; Ordered mesoporous material MCM-41 and 1,3-divinyl-1,1,3, the mol ratio of 3-tetramethyl-disilazane is 1:0.09; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The channel diameter that can be learnt prepared hydrophobicity meso-porous nano material by Fig. 6 is 2.3nm; The specific surface area that can be learnt prepared hydrophobicity meso-porous nano material by Fig. 7 is 1142m ²/ g; Can find out that by Fig. 8 prepared hydrophobicity meso-porous nano material has clear uniform meso-hole structure; Learn that through measuring the prepared contact angle of hydrophobicity meso-porous nano material behind compressing tablet is 140 degree.

The above-mentioned hydrophobicity meso-porous nano material and the β-CD that make are added in the entry by mass ratio 1:4, stir 48h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 14.35%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 56.63%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 92.1% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 30MHz in frequency, and intensity is 50W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 20 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 200 μ g/mL instead and continue to cultivate 12h, then use frequency to be 30MHz, intensity is 50W/cm ²Ultrasonic irradiation 12min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.23%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 200 μ g/mL, and after injecting 30min, use frequency to be 30MHz, intensity is 50W/cm ²UW property is according to 12min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 2.4% relatively.

Embodiment 3

With channel diameter is that 40nm, particle diameter are that 600nm, specific surface area are 300m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds tetramethyl-disilazane then, stirs 15h in 60 ℃; The mol ratio of ordered mesoporous material MCM-41 and tetramethyl-disilazane is 1:0.07; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:1, stir 48h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 12.3%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 38.6%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 94.2% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 15MHz in frequency, and intensity is 20W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 50 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 150 μ g/mL instead and continue to cultivate 12h, then use frequency to be 15MHz, intensity is 20W/cm ²Ultrasonic irradiation 14min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.36%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 150 μ g/mL, and after injecting 30min, use frequency to be 15MHz, intensity is 20W/cm ²UW property is according to 10min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 12.3% relatively.

Embodiment 4

With channel diameter is that 50nm, particle diameter are that 800nm, specific surface area are 150m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds chlorotriethyl silane then, stirs 10h in 25 ℃; The mol ratio of ordered mesoporous material MCM-41 and chlorotriethyl silane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:2, stir 10h in 25 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 8.6%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 30.26%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 90.25% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 0.5MHz in frequency, and intensity is 10W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 5 times, and is as shown in Figure 9.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 20 μ g/mL instead and continue to cultivate 12h, then use frequency to be 0.5MHz, intensity is 10W/cm ²Ultrasonic irradiation 8min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.86%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 20 μ g/mL, and after injecting 30min, use frequency to be 0.5MHz, intensity is 10W/cm ²UW property is according to 8min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 0.56% relatively.

Embodiment 5

With channel diameter is that 3nm, particle diameter are that 25nm, specific surface area are 2000m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds trimethylchlorosilane then, stirs 48h in 80 ℃; The mol ratio of ordered mesoporous material MCM-41 and trimethylchlorosilane is 1:0.08; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:0.2, stir 48h in 80 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 12.34%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 45.68%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 92.47% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 10MHz in frequency, and intensity is 10W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 95 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 60 μ g/mL instead and continue to cultivate 12h, then use frequency to be 10MHz, intensity is 10W/cm ²Ultrasonic irradiation 10min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 1.24%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 60 μ g/mL, and after injecting 30min, use frequency to be 10MHz, intensity is 10W/cm ²UW property is according to 10min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 10.21% relatively.

Embodiment 6

With channel diameter is that 5nm, particle diameter are that 50nm, specific surface area are 1500m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds hexamethyldisilazane then, stirs 24h in 25 ℃; The mol ratio of ordered mesoporous material MCM-41 and hexamethyldisilazane is 1:0.05; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Hydrophobicity meso-porous nano material that makes and tween-80 are added in the entry by mass ratio 1:0.3, stir 24h in 25 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 9.68%, the solubilizing agent tween-80 behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 42%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 95% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 1MHz in frequency, and intensity is 0.2W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 145 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 50 μ g/mL instead and continue to cultivate 12h, then use frequency to be 1MHz, intensity is 0.2W/cm ²Ultrasonic irradiation 8min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 4.7%.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 41.75% relatively.

Embodiment 7

With channel diameter is that 15nm, particle diameter are that 600nm, specific surface area are 500m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds 1 then, 3-divinyl-1,1,3, and the 3-tetramethyl-disilazane stirs 12h in 60 ℃; Ordered mesoporous material MCM-41 and 1,3-divinyl-1,1,3, the mol ratio of 3-tetramethyl-disilazane is 1:0.09; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Hydrophobicity meso-porous nano material that makes and hydroxypropyl are added in the entry by mass ratio 1:4, stir 48h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 14.35%, the solubilizing agent hydroxypropyl behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 56.63%.

Can be found out by fluorescence spectrum, be 30MHz in frequency, and intensity is 50W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 205 times.

Embodiment 8

With channel diameter is that 25nm, particle diameter are that 650nm, specific surface area are 350m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds tetramethyl-disilazane then, stirs 15h in 60 ℃; The mol ratio of ordered mesoporous material MCM-41 and tetramethyl-disilazane is 1:0.07; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Hydrophobicity meso-porous nano material that makes and γ-Huan Hujing are added in the entry by mass ratio 1:1, stir 28h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 12.3%, the solubilizing agent γ-Huan Hujing behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 38.6%.

Can be found out by fluorescence spectrum, be 15MHz in frequency, and intensity is 20W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 255 times.

Embodiment 9

With channel diameter is that 35nm, particle diameter are that 750nm, specific surface area are 1650m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds chlorotriethyl silane then, stirs 10h in 25 ℃; The mol ratio of ordered mesoporous material MCM-41 and chlorotriethyl silane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

With the hydrophobicity meso-porous nano material and 2,3 that makes, 6-fourth sulfo group sodium-beta-cyclodextrin adds in the entry by mass ratio 1:2, stirs 10h in 25 ℃, uses water washing then, and drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 8.6%; Solubilizing agent 2,3,6-fourth sulfo group sodium-beta-cyclodextrin behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 30.26%.

Can be found out by fluorescence spectrum, be 0.5MHz in frequency, and intensity is 10W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 215 times.

Embodiment 10

With channel diameter is that 45nm, particle diameter are that 350nm, specific surface area are 1450m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds 17 fluorine decyl Trimethoxy silanes then, stirs 10h in 25 ℃; The mol ratio of ordered mesoporous material MCM-41 and 17 fluorine decyl Trimethoxy silanes is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 8.6%; Solubilizing agent 2,3,6-fourth sulfo group sodium-beta-cyclodextrin behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 78%.

Can be found out by fluorescence spectrum, be 0.5MHz in frequency, and intensity is 100W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 255 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 20 μ g/mL instead and continue to cultivate 12h, then use frequency to be 0.5MHz, intensity is 100W/cm ²Ultrasonic irradiation 8min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.86%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 20 μ g/mL, and after injecting 30min, use frequency to be 0.5MHz, intensity is 100W/cm ²UW property is according to 8min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Embodiment 11

With channel diameter is that 15nm, particle diameter are that 250nm, specific surface area are 1850m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds hexamethyldisilazane then, stirs 24h in 25 ℃; The mol ratio of ordered mesoporous material MCM-41 and hexamethyldisilazane is 1:0.05; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 9.68%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 42%.

Can be found out by fluorescence spectrum, be 1MHz in frequency, and intensity is 300W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 140 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 50 μ g/mL instead and continue to cultivate 12h, then use frequency to be 1MHz, intensity is 300W/cm ²Ultrasonic irradiation 8min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.7%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 50 μ g/mL, and after injecting 30min, use frequency to be 1MHz, intensity is 300W/cm ²UW property is according to 5min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 1.75% relatively.

Embodiment 12

With channel diameter is that 6nm, particle diameter are that 100nm, specific surface area are 1050m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds 1 then, 3-divinyl-1,1,3, and the 3-tetramethyl-disilazane stirs 12h in 60 ℃; Ordered mesoporous material MCM-41 and 1,3-divinyl-1,1,3, the mol ratio of 3-tetramethyl-disilazane is 1:0.09; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:4, stir 48h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Can be found out by fluorescence spectrum, be 30MHz in frequency, and intensity is 600W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 200 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 200 μ g/mL instead and continue to cultivate 12h, then use frequency to be 30MHz, intensity is 600W/cm ²Ultrasonic irradiation 12min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.23%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 200 μ g/mL, and after injecting 30min, use frequency to be 30MHz, intensity is 600W/cm ²UW property is according to 12min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Embodiment 13

With channel diameter is that 15nm, particle diameter are that 250nm, specific surface area are 900m ²The ordered mesoporous material MCM-41 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds tetramethyl-disilazane then, stirs 15h in 60 ℃; The mol ratio of ordered mesoporous material MCM-41 and tetramethyl-disilazane is 1:0.07; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Can be found out by fluorescence spectrum, be 15MHz in frequency, and intensity is 900W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 50 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 150 μ g/mL instead and continue to cultivate 12h, then use frequency to be 15MHz, intensity is 900W/cm ²Ultrasonic irradiation 14min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.36%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 150 μ g/mL, and after injecting 30min, use frequency to be 15MHz, intensity is 900W/cm ²UW property is according to 10min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 1.3% relatively.

Embodiment 14

With channel diameter is that 5nm, particle diameter are that 50nm, specific surface area are 1500m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds tetramethyl-disilazane then, stirs 2h in 15 ℃; The mol ratio of ordered mesoporous material SBA-15 and tetramethyl-disilazane is 1:0.005; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The above-mentioned hydrophobicity meso-porous nano material and the β-CD that make are added in the entry by mass ratio 1:0.2, stir 48h in 35 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Can draw by Figure 10, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 4.35%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 51.68%.

Hydrophobicity meso-porous nano material is learnt the cytotoxicity experiment of ZR75-30 breast cancer cell after verifying described solubilising by the MTT detection method: the survival rate of cell explains that more than 94.34% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 0.1MHz in frequency, and intensity is 0.4W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 10 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 25 μ g/mL instead and continue to cultivate 12h, then use frequency to be 0.1MHz, intensity is 0.4W/cm ²Ultrasonic irradiation 20min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.14% (seeing shown in Figure 11).

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 25 μ g/mL, and after injecting 30min, use frequency to be 0.1MHz, intensity is 0.4W/cm ²UW property is according to 20min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 0.19% relatively.

Embodiment 15

With channel diameter is that 35nm, particle diameter are that 750nm, specific surface area are 1650m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds chlorotriethyl silane then, stirs 8h in 25 ℃; The mol ratio of ordered mesoporous material SBA-15 and chlorotriethyl silane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:3, stir 8h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 7.84%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 37.3%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 94.5% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 10MHz in frequency, and intensity is 20W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 25 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 80 μ g/mL instead and continue to cultivate 12h, then use frequency to be 10MHz, intensity is 20W/cm ²Ultrasonic irradiation 16min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 1.6%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 80 μ g/mL, and after injecting 30min, use frequency to be 10MHz, intensity is 20W/cm ²UW property is according to 15min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 10.6% relatively.

Embodiment 16

With channel diameter is that 6nm, particle diameter are that 100nm, specific surface area are 1050m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds trimethylchlorosilane then, stirs 6h in 40 ℃; The mol ratio of ordered mesoporous material SBA-15 and trimethylchlorosilane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:4, stir 6h in 40 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 4.23%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 21.35%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 98.56% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 45MHz in frequency, and intensity is 1.2W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 75 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 80 μ g/mL instead and continue to cultivate 12h, then use frequency to be 45MHz, intensity is 1.2W/cm ²Ultrasonic irradiation 6min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 40.23%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 80 μ g/mL, and after injecting 30min, use frequency to be 45MHz, intensity is 1.2W/cm ²UW property is according to 6min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 52.36% relatively.

Embodiment 17

With channel diameter is that 10nm, particle diameter are that 200nm, specific surface area are 100m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds hexamethyldisilazane then, stirs 12h in 25 ℃; The mol ratio of ordered mesoporous material SBA-15 and hexamethyldisilazane is 1:0.01; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Learn that through measuring the prepared contact angle of hydrophobicity meso-porous nano material behind compressing tablet is 120 degree.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:0.6, stir 4h in 25 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 6.3%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 29.56%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 98.35% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 2MHz in frequency, and intensity is 20W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 85 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 10 μ g/mL instead and continue to cultivate 12h, then use frequency to be 2MHz, intensity is 20W/cm ²Ultrasonic irradiation 12min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 2.35%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 10 μ g/mL, and after injecting 30min, use frequency to be 2MHz, intensity is 20W/cm ²UW property is according to 10min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 21.35% relatively.

Embodiment 18

With channel diameter is that 15nm, particle diameter are that 600nm, specific surface area are 500m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds 1 then, 3-divinyl-1,1,3, and the 3-tetramethyl-disilazane stirs 12h in 60 ℃; Ordered mesoporous material SBA-15 and 1,3-divinyl-1,1,3, the mol ratio of 3-tetramethyl-disilazane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:0.6, stir 12h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 6.5%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 26.48%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 96.48% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 6MHz in frequency, and intensity is 16W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 105 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 60 μ g/mL instead and continue to cultivate 12h, then use frequency to be 6MHz, intensity is 16W/cm ²Ultrasonic irradiation 6min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 6.58%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 60 μ g/mL, and after injecting 30min, use frequency to be 6MHz, intensity is 16W/cm ²UW property is according to 16min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 1.24% relatively.

Embodiment 19

With channel diameter is that 15nm, particle diameter are that 250nm, specific surface area are 1850m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds tetramethyl-disilazane then, stirs 2h in 15 ℃; The mol ratio of ordered mesoporous material SBA-15 and tetramethyl-disilazane is 1:0.005; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Husky nurse 188 is moored in the hydrophobicity meso-porous nano material that makes and Lip river add in the entry by mass ratio 1:0.2, stir 48h in 35 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 4.35%, the solubilizing agent Lip river moor husky nurse 188 behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 21.68%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 94.34% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 0.1MHz in frequency, and intensity is 0.4W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 55 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 25 μ g/mL instead and continue to cultivate 12h, then use frequency to be 0.1MHz, intensity is 0.4W/cm ²Ultrasonic irradiation 20min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.14%.

Embodiment 20

With channel diameter is that 50nm, particle diameter are that 800nm, specific surface area are 150m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds chlorotriethyl silane then, stirs 8h in 40 ℃; The mol ratio of ordered mesoporous material SBA-15 and chlorotriethyl silane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Hydrophobicity meso-porous nano material that makes and hydroxyethyl-are added in the entry by mass ratio 1:3, stir 8h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 7.84%, the solubilizing agent hydroxyethyl-behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 37.3%.

Can be found out by fluorescence spectrum, be 10MHz in frequency, and intensity is 20W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 235 times.

Embodiment 21

With channel diameter is that 2nm, particle diameter are that 20nm, specific surface area are 1000m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds trimethylchlorosilane then, stirs 6h in 40 ℃; The mol ratio of ordered mesoporous material SBA-15 and trimethylchlorosilane is 1:0.01; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Hydrophobicity meso-porous nano material that makes and sulfobutyl ether-beta-cyclodextrin are added in the entry by mass ratio 1:4, stir 6h in 40 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 4.23%, the solubilizing agent sulfobutyl ether-beta-cyclodextrin behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 21.35%.

Can be found out by fluorescence spectrum, be 45MHz in frequency, and intensity is 1.2W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 275 times.

Embodiment 22

With channel diameter is that 3nm, particle diameter are that 25nm, specific surface area are 2000m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds tetramethyl-disilazane then, stirs 2h in 15 ℃; The mol ratio of ordered mesoporous material SBA-15 and tetramethyl-disilazane is 1:0.005; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:0.2, stir 48h in 35 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 4.35%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 51.68%.

Can be found out by fluorescence spectrum, be 0.1MHz in frequency, and intensity is 400W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 100 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 25 μ g/mL instead and continue to cultivate 12h, then use frequency to be 0.1MHz, intensity is 400W/cm ²Ultrasonic irradiation 20min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.14%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 25 μ g/mL, and after injecting 30min, use frequency to be 0.1MHz, intensity is 400W/cm ²UW property is according to 20min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Embodiment 23

With channel diameter is that 45nm, particle diameter are that 350nm, specific surface area are 1450m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds chlorotriethyl silane then, stirs 8h in 25 ℃; The mol ratio of ordered mesoporous material SBA-15 and chlorotriethyl silane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Can be found out by fluorescence spectrum, be 10MHz in frequency, and intensity is 700W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 25 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 80 μ g/mL instead and continue to cultivate 12h, then use frequency to be 10MHz, intensity is 700W/cm ²Ultrasonic irradiation 16min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 1.6%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 80 μ g/mL, and after injecting 30min, use frequency to be 10MHz, intensity is 700W/cm ²UW property is according to 15min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 0.6% relatively.

Embodiment 24

With channel diameter is that 40nm, particle diameter are that 600nm, specific surface area are 300m ²The ordered mesoporous material SBA-15 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds trimethylchlorosilane then, stirs 6h in 40 ℃; The mol ratio of ordered mesoporous material SBA-15 and trimethylchlorosilane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Can be found out by fluorescence spectrum, be 45MHz in frequency, and intensity is 1kW/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 75 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 80 μ g/mL instead and continue to cultivate 12h, then use frequency to be 45MHz, intensity is 1kW/cm ²Ultrasonic irradiation 6min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 40.23%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 80 μ g/mL, and after injecting 30min, use frequency to be 45MHz, intensity is 1kW/cm ²UW property is according to 6min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 0.36% relatively.

Embodiment 25

With channel diameter is that 50nm, particle diameter are that 800nm, specific surface area are 150m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds trimethylchlorosilane then, stirs 36h in 0 ℃; The mol ratio of ordered mesoporous material MCM-48 and trimethylchlorosilane is 1:0.1; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:3, stir 36h in 50 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Can draw by Figure 12, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 7.56%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 45.7%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 93.23% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum shown in Figure 13, be 5MHz in frequency, and intensity is 0.6W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 15 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 5 μ g/mL instead and continue to cultivate 12h, then use frequency to be 5MHz, intensity is 0.6W/cm ²Ultrasonic irradiation 15min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.26%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 80 μ g/mL, and after injecting 30min, use frequency to be 5MHz, intensity is 0.6W/cm ²UW property is according to 18min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 12.56% relatively.

Embodiment 26

With channel diameter is that 35nm, particle diameter are that 750nm, specific surface area are 1650m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds hexamethyldisilazane then, stirs 16h in 60 ℃; The mol ratio of ordered mesoporous material MCM-48 and hexamethyldisilazane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:2, stir 16h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 6.3%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 50.2%.

Can be found out by fluorescence spectrum, be 25MHz in frequency, and intensity is 10W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 30 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 80 μ g/mL instead and continue to cultivate 12h, then use frequency to be 25MHz, intensity is 10W/cm ²Ultrasonic irradiation 12min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 2.1%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 80 μ g/mL, and after injecting 30min, use frequency to be 25MHz, intensity is 10W/cm ²UW property is according to 12min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 24.36% relatively.

Embodiment 27

With channel diameter is that 15nm, particle diameter are that 250nm, specific surface area are 900m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds 1 then, 3-divinyl-1,1,3, and the 3-tetramethyl-disilazane stirs 12h in 60 ℃; Ordered mesoporous material MCM-48 and 1,3-divinyl-1,1,3, the mol ratio of 3-tetramethyl-disilazane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:3, stir 12h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 12.36%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 49.63%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 95.6% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 6MHz in frequency, and intensity is 8W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 55 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 100 μ g/mL instead and continue to cultivate 12h, then use frequency to be 6MHz, intensity is 8W/cm ²Ultrasonic irradiation 10min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 2.35%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 100 μ g/mL, and after injecting 30min, use frequency to be 6MHz, intensity is 8W/cm ²UW property is according to 10min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 10.25% relatively.

Embodiment 28

With channel diameter is that 2nm, particle diameter are that 20nm, specific surface area are 1000m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds tetramethyl-disilazane then, stirs 8h in 20 ℃; The mol ratio of ordered mesoporous material MCM-48 and tetramethyl-disilazane is 1:0.1; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:4, stir 8h in 20 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 18.6%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 56.3%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 90.65% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 0.5MHz in frequency, and intensity is 45W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 65 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 20 μ g/mL instead and continue to cultivate 12h, then use frequency to be 0.5MHz, intensity is 45W/cm ²Ultrasonic irradiation 8min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.16%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 20 μ g/mL, and after injecting 30min, use frequency to be 0.5MHz, intensity is 45W/cm ²UW property is according to 6min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Embodiment 29

With channel diameter is that 15nm, particle diameter are that 250nm, specific surface area are 1850m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds chlorotriethyl silane then, stirs 48h in 100 ℃; The mol ratio of ordered mesoporous material MCM-48 and chlorotriethyl silane is 1:0.1; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and β-CD are added in the entry by mass ratio 1:5, stir 48h in 100 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 18.6%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 58.47%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 90.24% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 40MHz in frequency, and intensity is 40W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 125 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 200 μ g/mL instead and continue to cultivate 12h, then use frequency to be 40MHz, intensity is 40W/cm ²Ultrasonic irradiation 14min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 10.25%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 200 μ g/mL, and after injecting 30min, use frequency to be 40MHz, intensity is 40W/cm ²UW property is according to 14min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 0.98% relatively.

Embodiment 30

With channel diameter do? Do nm, particle diameter do? Do nm, specific surface area do? M ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds trimethylchlorosilane then, stirs 36h in 0 ℃; The mol ratio of ordered mesoporous material MCM-48 and trimethylchlorosilane is 1:0.1; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Hydrophobicity meso-porous nano material that makes and Yelkin TTS are added in the entry by mass ratio 1:3, stir 36h in 50 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 7.56%, solubilizing agent Yelkin TTS behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 45.7%.

Can be found out by fluorescence spectrum, be 5MHz in frequency, and intensity is 0.6W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 175 times.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 5 μ g/mL, and after injecting 30min, use frequency to be 5MHz, intensity is 0.6W/cm ²UW property is according to 18min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Embodiment 31

With channel diameter is that 5nm, particle diameter are that 50nm, specific surface area are 1500m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds hexamethyldisilazane then, stirs 16h in 60 ℃; The mol ratio of ordered mesoporous material MCM-48 and hexamethyldisilazane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Hydrophobicity meso-porous nano material that makes and alpha-cylodextrin are added in the entry by mass ratio 1:2, stir 16h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 6.3%, the solubilizing agent alpha-cylodextrin behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 50.2%.

Can be found out by fluorescence spectrum, be 25MHz in frequency, and intensity is 10W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 265 times.

Embodiment 32

With channel diameter is that 10nm, particle diameter are that 200nm, specific surface area are 100m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds 1 then, 3-divinyl-1,1,3, and the 3-tetramethyl-disilazane stirs 12h in 60 ℃; Ordered mesoporous material MCM-48 and 1,3-divinyl-1,1,3, the mol ratio of 3-tetramethyl-disilazane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and SANMALT-S-beta-cyclodextrin are added in the entry by mass ratio 1:3, stir 12h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 12.36%, solubilizing agent SANMALT-S-beta-cyclodextrin behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 49.63%.

Can be found out by fluorescence spectrum, be 6MHz in frequency, and intensity is 8W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 235 times.

Embodiment 33

With channel diameter is that 3nm, particle diameter are that 25nm, specific surface area are 2000m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds ten trifluoro octyl group Trimethoxy silanes then, stirs 16h in 60 ℃; The mol ratio of ordered mesoporous material MCM-48 and ten trifluoro octyl group Trimethoxy silanes is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Hydrophobicity meso-porous nano material that makes and sulfobutyl ether-beta-cyclodextrin are added in the entry by mass ratio 1:2, stir 16h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 6.3%, the solubilizing agent sulfobutyl ether-beta-cyclodextrin behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 50.2%.

Can be found out by fluorescence spectrum, be 25MHz in frequency, and intensity is 10W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 100 times.

Embodiment 34

With channel diameter is that 25nm, particle diameter are that 650nm, specific surface area are 350m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds trimethylchlorosilane then, stirs 36h in 0 ℃; The mol ratio of ordered mesoporous material MCM-48 and trimethylchlorosilane is 1:0.1; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Analyze by TG-DSC and to learn, have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 7.56%, solubilizing agent β-CD behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 45.7%.

Can be found out by fluorescence spectrum, be 5MHz in frequency, and intensity is 500W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 150 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 5 μ g/mL instead and continue to cultivate 12h, then use frequency to be 5MHz, intensity is 500W/cm ²Ultrasonic irradiation 15min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 0.26%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 80 μ g/mL, and after injecting 30min, use frequency to be 5MHz, intensity is 500W/cm ²UW property is according to 18min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 1.56% relatively.

Embodiment 35

With channel diameter is that 45nm, particle diameter are that 350nm, specific surface area are 1450m ²The ordered mesoporous material MCM-48 of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds hexamethyldisilazane then, stirs 16h in 60 ℃; The mol ratio of ordered mesoporous material MCM-48 and hexamethyldisilazane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Can be found out by fluorescence spectrum, be 25MHz in frequency, and intensity is 800W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 30 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 80 μ g/mL instead and continue to cultivate 12h, then use frequency to be 25MHz, intensity is 800W/cm ²Ultrasonic irradiation 12min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 2.1%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln that contains the above-mentioned FHMSN of 80 μ g/mL, and after injecting 30min, use frequency to be 25MHz, intensity is 800W/cm ²UW property is according to 12min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learnt that by experimental result after treatment, growth of tumor speed has had remarkable decline, the tumor propagation rate is 2.36% relatively.

Embodiment 36

With channel diameter is that 5nm, particle diameter are that 50nm, specific surface area are 1500m ²The spherical mesoporous Win 40350 of the ordered mesoporous material of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds hexamethyldisilazane then, stirs 24h in 25 ℃; The mol ratio of spherical mesoporous Win 40350 of ordered mesoporous material and hexamethyldisilazane is 1:0.01; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Can be found out by fluorescence spectrum, be 2MHz in frequency, and intensity is 20W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 285 times.

Embodiment 37

With channel diameter is that 40nm, particle diameter are that 600nm, specific surface area are 300m ²The spherical mesoporous Win 40350 of the ordered mesoporous material of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds 1 then, 3-divinyl-1,1,3, and the 3-tetramethyl-disilazane stirs 12h in 60 ℃; The spherical mesoporous Win 40350 of ordered mesoporous material and 1,3-divinyl-1,1,3, the mol ratio of 3-tetramethyl-disilazane is 1:0.06; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Hydrophobicity meso-porous nano material that makes and hydroxypropyl are added in the entry by mass ratio 1:0.6, stir 12h in 60 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 6.5%, the solubilizing agent hydroxypropyl behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 26.48%.

Verify that by the MTT detection method described FHMSN learns the cytotoxicity experiment of ZR75-30 breast cancer cell: the survival rate of cell explains that more than 96.348% above-mentioned FHMSN has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum, be 6MHz in frequency, and intensity is 16W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 35 times.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; Use the nutrient solution that contains the above-mentioned FHMSN of 60 μ g/mL instead and continue to cultivate 12h, then use frequency to be 6MHz, intensity is 16W/cm ²Ultrasonic irradiation 16min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 6.58%.

Embodiment 38

With channel diameter is that 45nm, particle diameter are that 350nm, specific surface area are 1450m ²The spherical mesoporous Win 40350 of the ordered mesoporous material of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds the trifluoro propyl triethoxyl silane then, stirs 12h in 25 ℃; The mol ratio of spherical mesoporous Win 40350 of ordered mesoporous material and trifluoro propyl triethoxyl silane is 1:0.01; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and hydroxypropyl-γ-Huan Hujing are added in the entry by mass ratio 1:0.6, stir 4h in 25 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 6.3%, solubilizing agent hydroxypropyl-γ-Huan Hujing behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 1.2%.

Can be found out by fluorescence spectrum, be 2MHz in frequency, and intensity is 20W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 75 times.

Embodiment 39

With channel diameter is that 2nm, particle diameter are that 20nm, specific surface area are 1000m ²The layered mesoporous Win 40350 of the ordered mesoporous material of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds tetramethyl-disilazane then, stirs 8h in 20 ℃; The mol ratio of layered mesoporous Win 40350 of ordered mesoporous material and tetramethyl-disilazane is 1:0.1; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Can be found out by fluorescence spectrum, be 0.5MHz in frequency, and intensity is 45W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 295 times.

Embodiment 40

With channel diameter is that 25nm, particle diameter are that 650nm, specific surface area are 350m ²The layered mesoporous Win 40350 of the ordered mesoporous material of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds chlorotriethyl silane then, stirs 48h in 100 ℃; The mol ratio of layered mesoporous Win 40350 of ordered mesoporous material and chlorotriethyl silane is 1:0.1; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

The hydrophobicity meso-porous nano material that makes and SANMALT-S-beta-cyclodextrin are added in the entry by mass ratio 1:5, stir 48h in 100 ℃, use water washing then, drying promptly gets hydrophobicity meso-porous nano material behind the solubilising, is designated as FHMSN.

Learn by the TG-DSC analysis; Have silane end group grafted group behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 18.6%, solubilizing agent SANMALT-S-beta-cyclodextrin behind solubilising in the hydrophobicity meso-porous nano material shared mass percent be 58.47%.

Can be found out by fluorescence spectrum, be 40MHz in frequency, and intensity is 40W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 55 times.

Embodiment 41

With channel diameter is that 6nm, particle diameter are that 100nm, specific surface area are 1050m ²The ordered mesoporous material MSU of/g adds in the reaction flask, adds normal hexane again it is fully disperseed, and adds trimethylchlorosilane then, stirs 48h in 80 ℃; The mol ratio of ordered mesoporous material MSU and trimethylchlorosilane is 1:0.08; Wash successively with normal hexane, ethanol then, dry under 30～200 ℃ again, promptly get hydrophobicity meso-porous nano material, be designated as HMSN.

Can be found out by fluorescence spectrum, be 10MHz in frequency, and intensity is 10W/cm ²Ultrasonic irradiation 2min under, above-mentioned FHMSN can improve the intensity of cavitation effect under the low intensity ultrasound effect significantly, cavitation intensity has increased by 225 times.

Comparative Examples 1

Learn through the laser confocal microscope checking: above-mentioned ordered mesoporous material MCM-41 all can normally be engulfed by tumour cell, does not cause the death of cell.

MCM-41 learns the cytotoxicity experiment of ZR75-30 breast cancer cell by the checking of MTT detection method: the survival rate of cell explains that more than 99.58% MCM-41 has good cell consistency and lower cytotoxicity.

Can be found out by fluorescence spectrum shown in Figure 14, be 1MHz in frequency, and intensity is 0.8W/cm ²Ultrasonic irradiation 2min under, MCM-41 can not improve the intensity of cavitation effect under the low intensity ultrasound effect.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum, inhales then and abandons nutrient solution, and the nutrient solution of using the MCM-41 that contains 50 μ g/mL instead continues to cultivate 12h, then uses frequency to be 1MHz, and intensity is 0.8W/cm ²Ultrasonic irradiation 8min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 98.56% (seeing shown in Figure 15).

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln of the MCM-41 that contains 50 μ g/mL, and after injecting 30min, use frequency to be 1MHz, intensity is 0.8W/cm ²UW property is according to 8min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learn that by experimental result without hydrophobically modified ordered mesoporous material MCM-41 and low-intensity ultrasonic coupling, the obvious restraining effect to tumor growth do not occur, the tumor propagation rate is 96.47% relatively.

Comparative Examples 2

Learn through the laser confocal microscope checking: above-mentioned order mesoporous nano material SBA-15 all can normally be engulfed by tumour cell, does not cause the death of cell.

SBA-15 learns the cytotoxicity experiment of ZR75-30 breast cancer cell by the checking of MTT detection method: the survival rate of cell explains that more than 98.6% SBA-15 has good cell consistency and lower cytotoxicity.

Can find out from fluorescence spectrum, be 0.1MHz in frequency, and intensity is 0.2W/cm ²Ultrasonic irradiation 2min under, SBA-15 can not improve the intensity of cavitation effect under the low intensity ultrasound effect.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; The nutrient solution of using the SBA-15 that contains 100 μ g/mL instead continues to cultivate 12h, then uses frequency to be 0.1MHz, and intensity is 0.2W/cm ²Ultrasonic irradiation 20min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 96.47%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln of the SBA-15 that contains 100 μ g/mL, and after injecting 30min, use frequency to be 0.1MHz, intensity is 0.2W/cm ²UW property is according to 20min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learn that by experimental result without hydrophobically modified ordered mesoporous material SBA-15 and low-intensity ultrasonic coupling, the obvious restraining effect to tumor growth do not occur, the tumor propagation rate is 92.34% relatively.

Comparative Examples 3

Learn through the laser confocal microscope checking: above-mentioned order mesoporous nano material MCM-48 all can normally be engulfed by tumour cell, does not cause the death of cell.

MCM-48 learns the cytotoxicity experiment of ZR75-30 breast cancer cell by the checking of MTT detection method: the survival rate of cell explains that more than 99.34% MCM-48 has good cell consistency and lower cytotoxicity.

Can find out from fluorescence spectrum, be 50MHz in frequency, and intensity is 50W/cm ²Ultrasonic irradiation 2min under, MCM-48 can not improve the intensity of cavitation effect under the low intensity ultrasound effect.

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum; Inhale then and abandon nutrient solution; The nutrient solution of using the MCM-48 that contains 200 μ g/mL instead continues to cultivate 12h, then uses frequency to be 50MHz, and intensity is 50W/cm ²Ultrasonic irradiation 10min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 96.57%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³, in tumour, to inject the physiological salt soln of the MCM-48 that contains 200 μ g/mL, and after injecting 30min, use frequency to be 50MHz, intensity is 50W/cm ²UW property is according to 10min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

Learn that by experimental result without hydrophobically modified ordered mesoporous material MCM-48 and low-intensity ultrasonic coupling, the obvious restraining effect to tumor growth do not occur, the tumor propagation rate is 96.54% relatively.

Comparative Examples 4

With ZR75-30 human breast cancer cell (1 * 10 ⁶Individual/mL, 1mL) transfer to 96 well culture plates, (RPMI1640+10% foetal calf serum) cultivated 24h in substratum, inhales then and abandons nutrient solution, uses the fresh nutrient solution that does not contain nano material instead and continues to cultivate 12h, then uses frequency to be 1MHz, and intensity is 0.2W/cm ²Ultrasonic irradiation 8min, continue to cultivate that to use mtt assay to record cell survival rate behind the 24h be 95.62%.

ZR75-30 human body breast cancer tumour is cut into 1mm ³Tissue be implanted in the nude mouse, treat that gross tumor volume is long to 100mm ³After, use frequency to be 1MHz, intensity is 0.2W/cm ²UW property is according to 5min at interval across water bag, this therapeutic process carries out once and carries out cubing every other day, carries out altogether 6 times.

A curve by among Fig. 5 can learn that this experimental group restraining effect do not occur to growth of tumor, and the tumor propagation rate is 97.68% relatively.

Comparative Examples 5

Separately in PBS solution, under the situation that does not add the nanometer material, be 50MHz in frequency, intensity is 50W/cm ²Ultrasonic irradiation 2min, can find out from fluorescence spectrum, under the irradiation of this intensity, cavitation intensity very a little less than, see shown in Figure 16.

To sum up result of study shows: hydrophobic nano mesoporous material provided by the invention and low-intensity ultrasonic have the obvious synergistic effect, can significantly strengthen low-intensity ultrasonic cavitation effect intensity; And have good cell consistency and a lower cytotoxicity; Especially behind solubilising, with the low-intensity ultrasonic coupling, in vivo with in the experiment in vitro effect of obvious suppression tumor growth is arranged all, have broad application prospects.

Be necessary at last in this explanation to be: above embodiment only is used for technical scheme of the present invention is done explanation in further detail; Can not be interpreted as the restriction to protection domain of the present invention, some nonessential improvement that those skilled in the art's foregoing according to the present invention is made and adjustment all belong to protection scope of the present invention.

Claims

1. hydrophobicity meso-porous nano material is characterized in that: by ordered mesoporous material and coupling reagent react and get, described coupling reagent is selected from any one in the following general formula:

Cl-SiR _{3 or}RO-SiR ₃, R group wherein includes the hydrophobicity organic group.

2. hydrophobicity meso-porous nano material according to claim 1 is characterized in that: described R group includes any one or a few hydrophobicity organic group that is selected from alkyl, alkylene, alkynes base, fluoroalkyl, the phenyl.

3. hydrophobicity meso-porous nano material according to claim 2; It is characterized in that: described coupling reagent is hexamethyldisilazane, tetramethyl-disilazane, 1; 3-divinyl-1; 1,3,3-tetramethyl-disilazane, trimethylchlorosilane, chlorotriethyl silane, ten trifluoro octyl group Trimethoxy silanes, trifluoro propyl triethoxyl silane or 17 fluorine decyl Trimethoxy silanes.

4. hydrophobicity meso-porous nano material according to claim 1 is characterized in that: the channel diameter of described ordered mesoporous material is that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m ²/ g.

5. hydrophobicity meso-porous nano material according to claim 4 is characterized in that: described ordered mesoporous material is MCM-41, MCM-48, SBA-15, MSU, spherical mesoporous Win 40350 or layered mesoporous Win 40350.

6. the described hydrophobicity meso-porous nano of claim 1 preparation methods is characterized in that, comprises the steps: under anhydrous condition, to make ordered mesoporous material and coupling reagent to carry out condensation reaction.

7. hydrophobicity meso-porous nano preparation methods according to claim 6; It is characterized in that; The operation of said condensation reaction is following: ordered mesoporous material is fully disperseed with organic solvent; Add coupling reagent then, under anhydrous condition, in 0～100 ℃ of stirring reaction 2～48 hours; Finish reaction, use organic solvent washing, drying; The mol ratio of ordered mesoporous material and coupling reagent is 1: (0.005～1).

8. hydrophobicity meso-porous nano preparation methods according to claim 7; It is characterized in that; The operation of said condensation reaction is following: ordered mesoporous material is fully disperseed with normal hexane, add coupling reagent then, under anhydrous condition, in 20～80 ℃ of stirring reactions 6～48 hours; Finish reaction, wash successively with normal hexane, ethanol, in 30～200 ℃ of dryings; The mol ratio of ordered mesoporous material and coupling reagent is 1: (0.01～0.1).

9. hydrophobicity meso-porous nano preparation methods according to claim 7 is characterized in that: it is that 2～50nm, particle diameter are that 20～800nm, specific surface area are 100～2000m that described ordered mesoporous material is selected from channel diameter ²Any one ordered mesoporous material in the MCM-41 of/g, MCM-48, SBA-15, MSU, spherical mesoporous Win 40350, the layered mesoporous Win 40350; Described coupling reagent is selected from hexamethyldisilazane, tetramethyl-disilazane, 1; 3-divinyl-1; 1; 3, any one in 3-tetramethyl-disilazane, trimethylchlorosilane, chlorotriethyl silane, ten trifluoro octyl group Trimethoxy silanes, trifluoro propyl triethoxyl silane, the 17 fluorine decyl Trimethoxy silanes.

10. hydrophobicity meso-porous nano preparation methods according to claim 9 is characterized in that: described ordered mesoporous material is prepared by hydrothermal method or template and gets.

11. the application of the described hydrophobicity meso-porous nano of claim 1 material is characterized in that: described hydrophobicity meso-porous nano material is incorporated in the low-intensity ultrasonic system, to strengthen low-intensity ultrasonic cavitation effect intensity; The frequency of described low-intensity ultrasonic is 0.1～50MHz, and intensity is 0.2～1000W/cm ²

12. the application of hydrophobicity meso-porous nano material according to claim 11 is characterized in that: at first adopt the described hydrophobicity meso-porous nano of solubilizing agent solubilising material, be incorporated into then in the low-intensity ultrasonic system.

13. the application of hydrophobicity meso-porous nano material according to claim 12; It is characterized in that; Adopt the operation of the described hydrophobicity meso-porous nano of solubilizing agent solubilising material following: hydrophobicity meso-porous nano material and solubilizing agent are added in the entry; Stir 2～48h at 0～100 ℃, use water washing then, drying; The mass ratio of hydrophobicity meso-porous nano material and solubilizing agent is 1: (0.2～5).

14. application according to claim 12 or 13 described hydrophobicity meso-porous nano materials; It is characterized in that: described solubilizing agent is selected from tween-80, Lip river and moors husky nurse 188, Yelkin TTS, hydroxypropyl-beta-cyclodextrin, hydroxyethyl-, alpha-cylodextrin, γ-Huan Hujing, sulfobutyl ether-beta-cyclodextrin, SANMALT-S-beta-cyclodextrin, 2; 3, any one in 6-fourth sulfo group sodium-beta-cyclodextrin, hydroxypropyl-alpha-cylodextrin, the hydroxypropyl-γ-Huan Hujing.