CN109550050A - A kind of molybdenum dioxide loading melanin carries medicine compound and its preparation and application - Google Patents
A kind of molybdenum dioxide loading melanin carries medicine compound and its preparation and application Download PDFInfo
- Publication number
- CN109550050A CN109550050A CN201910011359.1A CN201910011359A CN109550050A CN 109550050 A CN109550050 A CN 109550050A CN 201910011359 A CN201910011359 A CN 201910011359A CN 109550050 A CN109550050 A CN 109550050A
- Authority
- CN
- China
- Prior art keywords
- moo
- peg
- melanin
- preparation
- mel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0042—Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to a kind of molybdenum dioxide for loading melanin to carry medicine compound and its preparation and application, including MoO2Nanometer sheet, modification unit mPEG-DSPE, melanin and adriamycin.Preparation method includes: (1) by the mixing dispersion reaction of ammonium molybdate, ultrapure water, hydrochloric acid, hexamethylene and oleyl amine, obtains MoO2；(2) PEG is modified, MoO is obtained2-PEG；(3) melanin is loaded, MoO is obtained2-PEG-Mel；(4) load module drug DOX, obtains MoO2- PEG-Mel-DOX can be used for the synergistic treatment of breast cancer tumour.Preparation method of the present invention is easy to operate, and experiment condition is easy to control, the prospect with industrialized implementation.
Description
Technical field
The invention belongs to the molybdenum dioxide nano drug-carrying of medicament-carried nano field of material technology, in particular to load melanin is multiple
Close object and its preparation method and application.
Background technique
Malignant tumour seriously threatens human health and life, and the morbidity and mortality of tumour are continuously increased in recent years, swells
Tumor treatment has become the significant challenge that Medical research field is faced.Currently, the treatment means of tumour mainly with
Based on operation excision, radiation treatment and chemotherapy, certain tumours also using the methods of gene, biological therapy as
Adjuvant treatment.A kind of means of the chemotherapeutics as systemic therapy, can effectively to the invasion of antitumor cell and transfer, because
This chemotherapy is occupied an leading position in the comprehensive treatment of tumors.But traditional chemotherapeutics still remains certain limitation, example
Such as poorly water-soluble, the paracmasis is short, excretion is slow, apparent toxic side effect and the disadvantages of crossing drug resistant.Therefore this kind of chemicals
Therapeutic effect still have much room for improvement.In addition, photo-thermal therapy has better minimal invasive, treatment compared with traditional radiotherapy
The more preferable advantage of effect.
The appearance of nanotechnology provides new approaches for anti-tumor drug design.Nanotechnology merges multi-crossed disciplines association
Make, tumor imaging, diagnosing tumor and in terms of shown wide application prospect.Nanoscale twins carry medicine
System is easy to that surface targeting modification, circulation and residence time are long, easily penetrate into cell, sustained release can be achieved and control is released due to it
It the advantages such as puts, can overcome that biological selectivity present in existing small molecule drug formulation is poor, utilization rate is low, stability is poor, medicine
The defects of object action time is short, adverse reaction is serious.
It is worth noting that, the microenvironment of knub position is more slightly higher than the temperature of normal tissue, (1~2 DEG C is higher than normally
Tissue), slant acidity pH value (slightly below normal tissue) and the excess cell proliferation along with high enzyme concentration, these can all weaken carefully
The therapeutic effect of cytotoxic drugs.And the drug carrier system of some temperature or pH responsiveness can be synthesized according to these features,
Commonly known as " intelligent nano carrier ", because they can undergo quick, unexpected and reversible structure/attribute in knub position
Change, to cope with the minor change of ambient enviroment.
For molybdenum dioxide nano material due at low cost, optical absorption is wide, has photo-thermal therapy, pH response and carrying medicament
Ability, thus possess the great potential applied in biological medicine.Currently based on molybdenum dioxide control delivery research into one
Step reinforces photo-thermal therapy effect, while combining in research with chemotherapy, realizes the medicine-carried system of near infrared light and pH double-response,
The correlative study for improving therapeutic effect, reduction toxic side effect gradually causes scholars widely to pay close attention to.
Melanin is a kind of natural biological pigment, is almost distributed in all organisms, has extensive physiological function, is
The good targets of photoacoustic imaging, photo-thermal therapy, and can be carried out well with metal and drug huge legendary turtle and.Melanin is also a kind of good
Oxygen radical capturing agent, can be used to anti-oxidant, anti-aging, anti-radiation and uvioresistant etc..In addition, melanin also have it is disease-resistant
Poison adjusts the physiological functions such as immune, antitumor.Melanin has good biological degradability as a kind of natural biological pigment
And biocompatibility.In view of its special physicochemical property, melanin has a good application prospect in terms of medical consultations.Black
Element has strong absorption near infrared region, is a kind of good light thermit powder, can be used for photo-thermal therapy ablated tumor.Melanin can with very
Drug combines, as pharmaceutical carrier.As a kind of capturing agent, melanin can be used for anti-oxidant, anti-aging and anti-radiation etc..This
Outside, melanin is also used to treat disease relevant to short of melanin, such as senile dementia, xeroderma pitmentosum.
Wenyan Yin et al. has developed the optothermal material of molybdenum oxide nanoscale twins, the photo-thermal under 808nm laser irradiation
Transformation efficiency is 27.3% (Yin W, Bao T, Zhang X, et al.Biodegradable MoOx nanoparticles
with efficient near-infrared photothermal and photodynamic synergetic cancer
therapy at the second biological window[J].Nanoscale,2018,10.)。
Summary of the invention
Technical problem to be solved by the invention is to provide a kind of molybdenum dioxide nano drug-carrying compounds for loading melanin
And its preparation method and application, overcome the lower defect of photothermal conversion efficiency of oxidation molybdenum material.
A kind of molybdenum dioxide nano drug-carrying compound of load melanin of the invention, component include molybdenum dioxide MoO2It receives
Rice piece, modification unit polyethyleneglycol modified Distearoyl Phosphatidylethanolamine mPEG-DSPE, melanin and adriamycin DOX.
The present invention also provides the preparation methods of the molybdenum dioxide nano drug-carrying compound of above-mentioned load melanin, comprising:
(1) ammonium molybdate is distributed in ultrapure water, hydrochloric acid is added, ultrasound obtains ammonium molybdate dispersion liquid, oleyl amine is distributed to
Oleyl amine dispersion liquid is obtained in hexamethylene, is slowly added into ammonium molybdate dispersion liquid, then magnetic agitation is reacted, it is centrifuged, washing,
Obtain MoO2Material；Wherein, ammonium molybdate, oleyl amine mass ratio be 3:2-3:5, the volume ratio of ultrapure water, hydrochloric acid, hexamethylene is
30:1:10-30:1.5:13；
(2) MoO for obtaining step (1)2It is distributed in chloroform, ice-bath ultrasonic, mPEG-DSPE, room is then added
It is stirred overnight under temperature, rotates, wash and be centrifuged, obtain MoO2- PEG material；Wherein, MoO2Mass ratio with mPEG-DSPE is 1:
5-1:10；
(3) MoO for obtaining step (2)2- PEG is distributed in ultrapure water, then ultrasound is added melanin, continues to surpass
Sound is stirred overnight at room temperature, is centrifuged and is washed, obtains MoO2-PEG-Mel；Wherein, melanin and MoO2The mass ratio of-PEG is
1:5-1:10；
(4) MoO for obtaining step (3)2- PEG-Mel is mixed in ultrapure water with model drug DOX, is stirred at room temperature
Overnight, it is centrifuged and washs, obtain the molybdenum dioxide nano drug-carrying compound MoO of load melanin2-PEG-Mel-DOX；Wherein,
MoO2The mass ratio of-PEG-Mel and DOX is 1:1-1:3.
The concentration of hydrochloric acid is 1mol/L in the step (1).
The pH of ammonium molybdate dispersion liquid is 5.0-5.5 in the step (1).
The ultrasonic time is 5-10min in the step (1)；The magnetic agitation time is 0.5-1h.
The technological parameter reacted in the step (1) are as follows: reaction temperature is 180-260 DEG C, reaction time 12-15h.
The process conditions washed in the step (1) are as follows: using alternately washing 3-5 times of chloroform and ethyl alcohol.
The process conditions washed in the step (2), (3) and (4) are equal are as follows: use milli-Q water 3-5 times.
The time of ice-bath ultrasonic is 100-200min in the step (2).The purpose of ice-bath ultrasonic is by big nanometer sheet
Layer is processed into fractionlet, reduces particle size.
The ultrasonic time is 10-15min in the step (3).
The time for continuing ultrasound in the step (3) is 0.5-1h.
The present invention still further provides the molybdenum dioxide nano drug-carrying compound of above-mentioned load melanin in cancer target
And the application in synergistic treatment field.
Medicament-carried nano compound MoO produced by the present invention2The method that-PEG-Mel-DOX carries out drug release experiment, packet
It includes:
(1) DOX phosphate buffer solution and hac buffer are prepared, absorption maximum is detected in ultraviolet specrophotometer
Value, and the DOX standard curve being fitted under two kinds of pH environment；
(2) by MoO2- PEG-Mel-DOX carries medicine composite material and is dissolved in buffer solution, is placed in two bag filters, then
Bag filter is put into two kinds of pH value respectively and vibrates certain time, is sampled in different time points, and supplement buffer, pH is obtained and rings
Answer drug release patterns.
(3) by MoO2- PEG-Mel-DOX carries medicine composite material and is dissolved in acetate buffer solution, is placed in bag filter, so
It is sampled in different time points, and supplement buffer in different capacity irradiation certain time respectively afterwards, is obtained photothermal response drug
Release profiles.
The pH value of phosphate buffer solution is 7-7.5 in the step (1)；The pH value of hac buffer is 5-6.
DOX standard curve DOX concentration described in the step (1) is 0.005~0.08mg/mL.
Two kinds of pH value are respectively as follows: the acetic acid that phosphate buffer solution, pH value that pH value is 7-7.4 are 5-6 in the step (2)
Buffer solution；Duration of oscillation is that -72h, volume are 10-15mL for 24 hours.
MoO needed for drug release in the step (2)2It is 0.5~4mg that-PEG-Mel-DOX, which carries medicine composite material,.
MoO needed for drug release in the step (3)2It is 0.5~4mg, vinegar that-PEG-Mel-DOX, which carries medicine composite material,
The pH value of acid buffering solution is 5-6；The wavelength of laser is 808nm, irradiation power 1.0-3.0W/cm2, irradiation time 1-
5min；Duration of oscillation is that -72h, volume are 10-15mL for 24 hours.
The present invention modifies molybdenum dioxide by PEG, has the function that increase load medicine complex stabilities.Pass through near infrared light
Irradiation so that carrying after medicine compound enters cell by endocytic pathway, because local heating caused by photo-thermal effect makes inner body
Film is unstable, so that drug and its carrier be promoted to escape from endosome.Reaching most of anticancer drugs should be promptly released into carefully
Effect in cell lysis matter.To greatly improve the curative effect of drug.The present invention constructs the synergistic treatment system of chemotherapy and photo-thermal therapy,
The photothermal conversion efficiency of optothermal material molybdenum dioxide is further increased by loading the good melanin of biocompatibility.
Beneficial effect
(1) method of the invention is simple, and reaction condition is mild, easily operated, the prospect with industrialized implementation.
(2) MoO of the invention2It is high that-PEG-Mel-DOX carries medicine composite material drug load, can long-acting slow-release, and have
There are pH and near infrared light double-bang firecracker to answer conveying capacity, release rate is high under lower ph environment, is suitble to the microenvironment of tumor tissues；And
Hyperthermia is generated under the laser irradiation of lower-wattage, the potentiality with tumour long-acting slow-release.
(3) nano particle that the present invention obtains has preferable water dispersible and biocompatibility, has and is applied to tumour
The prospect of targeting and synergistic treatment.
(4) MoO of the invention2- PEG-Mel-DOX carry the melanin that loads in medicine composite material may be implemented to enhance its it is right
The photo-thermal therapy effect of breast cancer cell, photothermal conversion efficiency can achieve 69.1%.
Detailed description of the invention
Fig. 1 is the TEM map of molybdenum dioxide nanometer sheet in embodiment 1；
Fig. 2 is MoO in embodiment 12、MoO2-PEG、MoO2-PEG-Mel、MoO2The uv-spectrogram of-PEG-Mel-DOX；
Fig. 3 is MoO in embodiment 12、PEG、MoO2-PEG、Mel、MoO2-PEG-Mel、DOX、MoO2-PEG-Mel-DOX
Infared spectrum；
Fig. 4 is MoO in embodiment 12、MoO2-PEG、MoO2-PEG-Mel、MoO2The Zeta electric potential of-PEG-Mel-DOX becomes
Change；
Fig. 5 is MoO in embodiment 12The hydrodynamics diameter change of-PEG material；
Fig. 6 is MoO in embodiment 22The vitro drug release behavior of-PEG-Mel-DOX in different condition.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
Embodiment 1
(1) 3g ammonium molybdate is distributed in 30ml ultrapure water, 1ml hydrochloric acid (concentration 1mol/L) is added later, at ultrasound
Reason five minutes, 2g oleyl amine is distributed in 10ml hexamethylene, oleyl amine dispersion liquid is slowly added into ammonium molybdate dispersion liquid, magnetic force
Half an hour is stirred, product is reacted 15 hours at 200 DEG C, product is collected after reaction and is centrifuged, use chloroform later
With ethanol washing and collect, obtain molybdenum dioxide material.
(2) the molybdenum dioxide material that step (1) is prepared is distributed in 50ml chloroform soln, later to solution
It carries out ice-bath ultrasonic process 150 minutes, big nanoscale twins is processed into fractionlet, reduce particle size.After ultrasonic treatment,
The mPEG-DSPE of 500mg is added, is stirred overnight at room temperature, evaporates chloroform using revolving method, obtains dark-brown dry matter,
And with milli-Q water and product is collected by centrifugation, obtain MoO2- PEG material.
(3) by MoO made from step (2)2- PEG material is distributed in 50ml ultrapure water, and is ultrasonically treated ten minutes, it
The melanin that mass ratio is 10:1 is added afterwards, mixed solution is ultrasonically treated half an hour, is stirred at room temperature overnight, Zhi Houli
The heart collects product and with milli-Q water, finally collects product, obtains MoO2-PEG-Mel。
(4) MoO for obtaining step (3)2- PEG-Mel is mixed in ultrapure water with model drug DOX with mass ratio 1:1
Afterwards and the processing that is stirred overnight at room temperature, it is centrifuged simultaneously multiple with milli-Q water, finally collects product, load the molybdenum dioxide of melanin
Nano drug-carrying compound MoO2-PEG-Mel-DOX。
Supernatant is collected by centrifugation and tests the absorbance of supernatant,
By the final product MoO of the present embodiment2- PEG-Mel-DOX is distributed in ultrapure water, shoots TEM, as a result such as Fig. 1
It is shown, observe form, it is known that be successfully prepared the more uniform nanoscale twins material of form.
Structural identification is carried out to the products at different levels of the present embodiment, measurement carries MoO before and after medicine2、MoO2-PEG、MoO2-PEG-
Mel、MoO2The ultraviolet absorptivity of four kinds of materials of-PEG-Mel-DOX, uv-spectrogram variation are as shown in Figure 2, it is known that have at 270nm
The characteristic peak of melanin has the characteristic peak of DOX at 480nm, it was demonstrated that melanin and DOX's is successfully loaded.
Further to MoO before and after load medicine2、MoO2-PEG、MoO2-PEG-Mel、MoO2Four kinds of materials of-PEG-Mel-DOX into
Row IR Characterization, infared spectrum variation are as shown in Figure 3, it is known that 1067cm-1And 958cm-1The successful load of PEG, passes through known to place
1705cm-1And 1607cm-1The successful load of melanin, passes through 1577cm known to place-1And 1620cm-1The success of DOX is negative known to place
It carries.
Physicochemical property test is carried out to the product of synthesis, measurement carries MoO before and after medicine2、MoO2-PEG、MoO2-PEG-Mel、
MoO2The potential change of four kinds of materials of-PEG-Mel-DOX, as a result as shown in Figure 4, it is known that potential changes before and after material, auxiliary
The successful preparation of the bright different phase material of corroborative evidence, while biggish absolute value shows the favorable dispersibility of material.
Further to MoO2- PEG material carries out the detection of DLS, and hydrodynamics diameter result is as shown in Figure 5, it is known that material
The particle size of material meets EPR effect in 160 ± 10nm, is conducive to material passive target and is gathered in tumor region, can prove
Material successfully synthesizes.
Embodiment 2
MoO of the invention2The method of-PEG-Mel-DOX medicine-carried system progress drug release experiment:
(1) DOX phosphate buffer solution and hac buffer are prepared, absorption maximum is detected in ultraviolet specrophotometer
Value, and it is fitted the DOX standard curve of (5.8,7.4) under two kinds of pH environment；
(2) by 5mg MoO2- PEG-Mel-DOX carries medicine composite material and is dissolved in 5mL buffer solution, is placed in two bag filters
In, then bag filter is placed in the buffer solution of pH 5.8 and pH 7.0 respectively and is vibrated, is sampled in different time points, supplement is new
Fresh buffer obtains pH response medicine release profiles.
(3) by 5mgMoO2- PEG-Mel-DOX carries medicine composite material and is dissolved in 5mL difference pH buffer solution (5.8 Hes respectively
7.4) it in, is placed in bag filter, then uses 808nm 1W/cm respectively2Laser irradiation 5min, be subsequently placed in shaking table and vibrate,
It is detected from different point in time sampling, and supplements buffer, obtain photothermal response drug release patterns.
DOX is under two kinds of pH environment and whether there is or not the release profiles under laser irradiation condition are as shown in Figure 6, it is seen that under different pH
There are significant differences for release, and photo-thermal is remarkably improved the release of drug, and tumor tissues are wanted compared with normal tissue cell compared to its pH
Low, the release of the medicine carrying material conforms exactly to this characteristic.Show that the load medicine composite material is that one kind can be used for oncotherapy
PH/ light multiple stimulation response type pharmaceutical carrier.
Comparative example 1
Wenyan Yin et al. has developed the optothermal material of molybdenum oxide nanoscale twins, the photo-thermal under 808nm laser irradiation
Transformation efficiency is 27.3% (Yin W, Bao T, Zhang X, et al.Biodegradable MoOx nanoparticles
with efficient near-infrared photothermal and photodynamic synergetic cancer
therapy at the second biological window[J].Nanoscale,2018,10.)。
And in the present invention, the preparation of molybdenum oxide nanoscale twins is modified, and load melanin and further strengthen material
The photo-thermal effect of material, photothermal conversion efficiency can achieve 69.1%, and then reinforcing material is for the therapeutic effect of tumour.
Claims (10)
1. a kind of molybdenum dioxide nano drug-carrying compound for loading melanin, component includes molybdenum dioxide MoO2Nanometer sheet, modification are single
Member polyethyleneglycol modified Distearoyl Phosphatidylethanolamine mPEG-DSPE, melanin Mel and adriamycin DOX.
2. a kind of preparation method of the molybdenum dioxide nano drug-carrying compound of load melanin as described in claim 1, comprising:
(1) ammonium molybdate is distributed in ultrapure water, hydrochloric acid is added, ultrasound obtains ammonium molybdate dispersion liquid, oleyl amine is distributed to hexamethylene
Oleyl amine dispersion liquid is obtained in alkane, is slowly added into ammonium molybdate dispersion liquid, and then magnetic agitation is reacted, be centrifuged, and washing obtains
MoO2Material；Wherein, ammonium molybdate, oleyl amine mass ratio be 3:2-3:5, the volume ratio of ultrapure water, hydrochloric acid, hexamethylene is 30:1:
10-30:1.5:13；
(2) MoO for obtaining step (1)2It is distributed in chloroform, ice-bath ultrasonic, mPEG-DSPE is then added, stirs at room temperature
It mixes overnight, revolving is washed and is centrifuged, obtains MoO2- PEG material；Wherein, MoO2Mass ratio with mPEG-DSPE is 1:5-1:
10；
(3) MoO for obtaining step (2)2- PEG is distributed in ultrapure water, then melanin is added in ultrasound, continues ultrasound, room temperature
Under be stirred overnight, be centrifuged and wash, obtain MoO2-PEG-Mel；Wherein, melanin and MoO2The mass ratio of-PEG is 1:5-1:
10；
(4) MoO for obtaining step (3)2- PEG-Mel is mixed in ultrapure water with model drug DOX, is stirred overnight at room temperature,
It is centrifuged and washs, obtain the molybdenum dioxide nano drug-carrying compound MoO of load melanin2-PEG-Mel-DOX；Wherein, MoO2-
The mass ratio of PEG-Mel and DOX is 1:1-1:3.
3. preparation method according to claim 2, it is characterised in that: the concentration of hydrochloric acid is 1mol/L in the step (1)；
The pH of ammonium molybdate dispersion liquid is 5.0-5.5.
4. preparation method according to claim 2, it is characterised in that: the ultrasonic time is 5- in the step (1)
10min；The magnetic agitation time is 0.5-1h.
5. preparation method according to claim 2, it is characterised in that: the technological parameter reacted in the step (1) are as follows: anti-
Answering temperature is 180-260 DEG C, reaction time 12-15h.
6. preparation method according to claim 2, it is characterised in that: the process conditions washed in the step (1) are as follows: adopt
With alternately washing 3-5 times of chloroform and ethyl alcohol.
7. preparation method according to claim 2, it is characterised in that: the technique washed in the step (2), (3) and (4)
Condition is equal are as follows: uses milli-Q water 3-5 times.
8. preparation method according to claim 2, it is characterised in that: the time of ice-bath ultrasonic is in the step (2)
100-200min。
9. preparation method according to claim 2, it is characterised in that: the ultrasonic time is 10- in the step (3)
15min；The time for continuing ultrasound is 0.5-1h.
10. the molybdenum dioxide nano drug-carrying compound of load melanin described in claim 1 is in cancer target and synergistic treatment
Application in field.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910011359.1A CN109550050B (en) | 2019-01-07 | 2019-01-07 | Melanin-loaded molybdenum dioxide drug-loaded compound and preparation and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910011359.1A CN109550050B (en) | 2019-01-07 | 2019-01-07 | Melanin-loaded molybdenum dioxide drug-loaded compound and preparation and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109550050A true CN109550050A (en) | 2019-04-02 |
| CN109550050B CN109550050B (en) | 2021-08-31 |
Family
ID=65872456
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910011359.1A Active CN109550050B (en) | 2019-01-07 | 2019-01-07 | Melanin-loaded molybdenum dioxide drug-loaded compound and preparation and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109550050B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114246946A (en) * | 2021-12-27 | 2022-03-29 | 重庆医科大学附属第一医院 | Nano contrast agent for diagnosis and treatment integration and preparation method thereof |
| CN114246956A (en) * | 2021-12-27 | 2022-03-29 | 重庆医科大学附属第一医院 | Oxygen-deficient iron-molybdenum oxide flower-like nanoparticles for diagnosis and treatment integration and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104371714A (en) * | 2014-11-28 | 2015-02-25 | 赵兵 | Molybdenum trioxide-graphene oxide composite material and preparation method thereof |
| CN106390120A (en) * | 2016-11-03 | 2017-02-15 | 中国人民解放军第三军医大学第三附属医院 | Magnetic nanometer material used for imaging and photothermal therapy and preparation method and application of magnetic nanometer material |
| WO2017061673A1 (en) * | 2015-10-06 | 2017-04-13 | 전남대학교 산학협력단 | Photothermal therapy composition using melanin, and preparation method therefor |
| CN106938857A (en) * | 2017-03-01 | 2017-07-11 | 南京理工大学 | A kind of molybdenum dioxide nanometer optical-thermal conversion material and its preparation method and application |
| CN108837158A (en) * | 2018-08-09 | 2018-11-20 | 东华大学 | A kind of molybdenum disulfide nano carries medicine compound and its preparation method and application |
-
2019
- 2019-01-07 CN CN201910011359.1A patent/CN109550050B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104371714A (en) * | 2014-11-28 | 2015-02-25 | 赵兵 | Molybdenum trioxide-graphene oxide composite material and preparation method thereof |
| WO2017061673A1 (en) * | 2015-10-06 | 2017-04-13 | 전남대학교 산학협력단 | Photothermal therapy composition using melanin, and preparation method therefor |
| CN106390120A (en) * | 2016-11-03 | 2017-02-15 | 中国人民解放军第三军医大学第三附属医院 | Magnetic nanometer material used for imaging and photothermal therapy and preparation method and application of magnetic nanometer material |
| CN106938857A (en) * | 2017-03-01 | 2017-07-11 | 南京理工大学 | A kind of molybdenum dioxide nanometer optical-thermal conversion material and its preparation method and application |
| CN108837158A (en) * | 2018-08-09 | 2018-11-20 | 东华大学 | A kind of molybdenum disulfide nano carries medicine compound and its preparation method and application |
Non-Patent Citations (5)
| Title |
|---|
| GUOSHENG SONG ET AL: ""Degradable Molybdenum Oxide Nanosheets with Rapid Clearance and Efficient Tumor Homing Capabilities as a Therapeutic Nanoplatform"", 《ANGEW. CHEM. INT. ED》 * |
| LIANG ZHANG ET AL: ""Bioinspired Multifunctional Melanin-Based Nanoliposome for Photoacoustic/Magnetic ResonanceImaging-Guided Efficient Photothermal Ablation of Cancer"", 《THERANOSTICS》 * |
| XINYU WANG ET AL: ""Multi-responsive photothermal-chemotherapy with drug-loaded melanin-like nanoparticles for synergetic tumor ablation"", 《BIOMATERIALS》 * |
| 姜琴 等: ""多模影像指导的功能化纳米黑色素靶向乳腺癌的光热治疗"", 《2016年全国高分子材料科学与工程研讨会论文摘要集》 * |
| 李昱 等: ""多功能二氧化钼纳米载药平台制备及药物释放研究"", 《化工新型材料》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114246946A (en) * | 2021-12-27 | 2022-03-29 | 重庆医科大学附属第一医院 | Nano contrast agent for diagnosis and treatment integration and preparation method thereof |
| CN114246956A (en) * | 2021-12-27 | 2022-03-29 | 重庆医科大学附属第一医院 | Oxygen-deficient iron-molybdenum oxide flower-like nanoparticles for diagnosis and treatment integration and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109550050B (en) | 2021-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107875158B (en) | Preparation method of carrier-free nano-drug with chemotherapy/phototherapy | |
| CN108815524B (en) | Hyaluronic acid modified polypyrrole coated drug-loaded phase change material photo-thermal therapeutic agent and preparation method thereof | |
| CN106729742B (en) | A kind of cancer target sericin micella and its preparation method and application | |
| CN104043135A (en) | Albumin indocyanine green paclitaxel compound as well as preparation method and application thereof | |
| CN107812200B (en) | BSA-gadolinium ionic complex-coated hollow gold nanosheet and preparation method thereof | |
| Zhang et al. | NIR light-induced tumor phototherapy using photo-stable ICG delivery system based on inorganic hybrid | |
| CN113751079B (en) | Perovskite-titanium dioxide nano composite photocatalyst loaded by biological material and construction method and application thereof | |
| CN110193087A (en) | A kind of tumor microenvironment response type diagnosis and treatment integration nano-probe and preparation method thereof | |
| CN111760024A (en) | Permeation enhanced gold nanocluster drug-loaded targeting preparation and preparation method and application thereof | |
| CN112972423A (en) | Cascade reaction-based nano enzyme and chemotherapeutic drug co-loaded bionic nano drug carrier and preparation method and application thereof | |
| CN109550050A (en) | A kind of molybdenum dioxide loading melanin carries medicine compound and its preparation and application | |
| CN110755640B (en) | Preparation method and application of gold-platinum composite nano diagnosis and treatment agent | |
| CN111407743A (en) | Dopamine assembly drug delivery system and preparation method thereof | |
| He et al. | Polymyxin E biomineralized and doxorubicin-loaded gold nanoflowers nanodrug for chemo-photothermal therapy | |
| CN110623940A (en) | Selenium/silicon dioxide/gold nano composite particle and preparation method and application thereof | |
| CN114099674A (en) | Copper or zinc carrier carrying diethyl dithiocarbamate prodrug, preparation and application | |
| CN110882389B (en) | Titanium monoxide nano material and preparation method and application thereof | |
| Zhao et al. | TPGS and cypate gated mesoporous carbon for enhanced thermochemotherapy of tumor | |
| CN109650449B (en) | Preparation method of molybdenum oxide nano material, product and application | |
| CN112546025A (en) | Preparation method of Ce6@ CMCS-DSP-IPI549 antitumor nano-delivery system | |
| CN103990124A (en) | Graphene nanocomposite particle used for multimodal imaging/photodynamic therapy, and preparation method and application thereof | |
| CN115025065B (en) | Stimulation-responsive multifunctional targeted micro robot and preparation method and application thereof | |
| CN114177289B (en) | Composite nano material for photodynamic and photothermal combined treatment and preparation method and application thereof | |
| CN110917172B (en) | Molybdenum oxide nanosheet plugging hollow mesoporous silicon nanomaterial and preparation and application thereof | |
| CN110251689A (en) | A kind of chitosan nano-material and preparation method thereof for lung cancer therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |