CN103961318A - Nano-administration system for inhibiting multi-drug resistance breast cancer growth, preparation method and application thereof - Google Patents
Nano-administration system for inhibiting multi-drug resistance breast cancer growth, preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to the technical field of breast cancer, and discloses a preparation method of a nano-administration system for inhibiting multi-drug resistance breast cancer growth. According to the system, mesoporous silica nano-particles are used as a carrier, and chemotherapeutic medicaments and CD44 monoclonal antibody are loaded at the same time. The invention also discloses a CD44 monoclonal antibody IM7, which has an inhibiting effect on multi-drug resistance breast cancer cells for the first time, wherein the inhibition effect on the multi-drug resistance breast cancer can be reinforced by further loading the CD44 monoclonal antibody IM7 onto the nano-administration system, and the retention volume of the chemotherapeutic medicaments in the multi-drug resistance breast cancer tissue can be remarkably increased by virtue of the nano-administration system loaded with the chemotherapeutic medicaments and the CD44 monoclonal antibody IM7, the multi-drug resistance breast cancer growth can be effectively inhibited, and the curative effect on multi-drug resistance breast cancer can be remarkably improved.
Description
Technical field
The present invention relates to breast cancer treatment field, be specifically related to a kind of administration nano-drug administration system that can suppress multidrug resistance growth of breast cancers and preparation method thereof and application.
Background technology
Breast carcinoma is the modal malignant tumor of whole world women, serious threat human life health
[1].Therefore in the urgent need to the effective ways of breast cancer treatment.Breast carcinoma multidrug resistance is the main cause of chemotherapy failure, and can cause recurrence and shift, and becomes the biggest obstacle of oncotherapy.The resistance mechanism complexity of breast cancer cell and breast carcinoma stem cell, relates to several drug resistance-associated proteins, and wherein CD44 (cluster of differentiation44) molecule is the key molecule of breast carcinoma drug resistance.CD44, is a kind of cell surface adhesion molecule of being encoded by single-gene, and CD44 molecule high expressed is in the tumor cell of several drug resistance and the cell membrane of tumor stem cell
[2], CD44 molecule not only contributes to Mdr-p MDR1 that chemotherapeutics is pumped in cell, reduces the effective dose of medicine in tumor cell
[3]; Also contribute to transfer and the diffusion of drug-resistant tumor cell
[4], cause failing to respond to any medical treatment and prognosis mala of clinical tumor patient
[5].At present carry out the research of oncotherapy in the monoclonal antibody of also not applying CD44 molecule aspect the treatment of drug-resistant tumor.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of administration nano-drug administration system that suppresses multidrug resistance growth of breast cancers.
The technical problem that the present invention also will solve is to provide the preparation method of above-mentioned administration nano-drug administration system.
The technical problem that the present invention finally will solve is to provide the application of above-mentioned administration nano-drug administration system.
For solving the problems of the technologies described above, the technical solution used in the present invention is as follows:
Suppress an administration nano-drug administration system for multidrug resistance growth of breast cancers, it loads chemotherapeutics and CD44 monoclonal antibody taking mesoporous silicon dioxide nano particle as carrier simultaneously.
Wherein, described mesoporous silicon dioxide nano particle seed footpath is 20-200nm, and pattern is spherical, oval or cylindrical.
Wherein, described mesoporous silicon dioxide nano particle can also can directly be bought from the market in own preparation, as long as meet above-mentioned particle diameter and pattern requirement.If preparation voluntarily, preparation method can be with silylating reagent under the catalysis of catalyst mutually polycondensation form evenly continuously, the mesoporous material of high-sequential.Regulate different constituent, add reagent and ratio thereof and can obtain mesoporous silicon dioxide nano particle of different size, pattern, pattern be can be for spherical, ellipse, and cylindrical grade is regardless of, and has mesopore orbit and stores up and receive space as medicine.Can prepare by list of references [6].
Wherein, described chemotherapeutics is mammary cancer chemotherapy medicine.
Wherein, described chemotherapeutics is any one or a few the combination in amycin, paclitaxel and cisplatin.
Wherein, described CD44 monoclonal antibody is CD44 monoclonal antibody IM7.
The preparation method of the administration nano-drug administration system of above-mentioned inhibition multidrug resistance growth of breast cancers, the method comprises the steps:
(1) prepare or buy monodispersed mesoporous silicon dioxide nano particle, particle diameter is 20-100nm, and pattern is spherical, oval or cylindrical;
(2) mesoporous silicon dioxide nano particle sub-surface step (1) being obtained carries out amino or carboxyl functional group is modified;
(3) mesoporous silicon dioxide nano particle after step (2) is modified carries out the loading of CD44 monoclonal antibody, the administration nano-drug administration system of preparation coupling CD44 monoclonal antibody;
(4) administration nano-drug administration system of coupling CD44 monoclonal antibody step (3) being obtained loads chemotherapeutics, prepares the administration nano-drug administration system that suppresses multidrug resistance growth of breast cancers.
In step (1), described monodispersed mesoporous silicon dioxide nano particle can also can directly be bought from the market in own preparation, as long as meet above-mentioned monodispersity, particle diameter and pattern requirement.If preparation voluntarily, preparation method can be with silylating reagent under the catalysis of catalyst mutually polycondensation form evenly continuously, the mesoporous material of high-sequential.Regulate different constituent, add reagent and ratio thereof and can obtain mesoporous silicon dioxide nano particle of different size, pattern, pattern be can be for spherical, ellipse, and cylindrical grade is regardless of, and has mesopore orbit and stores up and receive space as medicine.Can list of references
[6]prepare.
In step (2), adopt 3-aminopropyl triethoxysilane to carry out amido modified to mesoporous silicon dioxide nano particle sub-surface; Or adopt glutaric anhydride to carry out carboxyl modified to mesoporous silicon dioxide nano particle sub-surface.
In step (3), utilize 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxy-succinamide activation system by the activated carboxylic on CD44 monoclonal antibody IM7, then carry out being connected of antibody I M7 with amido modified mesoporous silicon dioxide nano particle by condensation reaction; Or utilize 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxy-succinamide activation system by the mesoporous silicon dioxide nano particle activation of carboxyl modified, then carry out being connected of antibody I M7 with the amino on CD44 monoclonal antibody IM7 by condensation reaction.
In step (4), utilize the electrostatic interaction and the hydrogen bonding effect that between the administration nano-drug administration system of coupling CD44 monoclonal antibody and chemotherapeutics (as amycin), exist to carry out medicine carrying.
The administration nano-drug administration system of above-mentioned inhibition multidrug resistance growth of breast cancers suppresses the application in multidrug resistance breast cancer cell growth medicine in preparation.
In the research of reversing multiple medicine resistance of tumor cells, find that nano medicament carrying system is applied to oncotherapy, can increase the concentration of chemotherapeutics in tumor, overcome tumor drug resistance.Its mechanism of action may be that nano medicament carrying system has changed medicine and originally entered the approach of tumor cell, thereby has avoided identification, combination and the outer row of the albumen that multidrug resistance is relevant, makes medicine accumulate increase intracellular
[7].The coupling CD44 monoclonal antibody IM7 that we prepare carries the administration nano-drug administration system of chemotherapeutics, utilize receptor (CD44) and part (IM7) in conjunction with having advantages of that specificity is good, affinity is strong, administration nano-drug administration system is combined with drug resistance breast cancer cell, medicine accurately can be delivered to drug resistance breast cancer cell, reach and strengthen the picked-up of drug resistance breast cancer cell to chemotherapeutics, reduce the object of the toxic and side effects of normal tissue.The more important thing is, using nanoparticle as administration platform, strengthened on the one hand the sealing process of CD44 antibody; Strengthen on the other hand the fragmentation effect of chemotherapeutics to drug resistance breast cancer cell.Administration nano-drug administration system multiple action of the present invention, in drug resistance breast cancer cell, has improved targeting and the sensitivity for the treatment of, has reduced the consumption of toxicity chemotherapeutics, has significantly strengthened the curative effect for the treatment of drug resistance breast carcinoma.
List of references:
[1]Siegel R,Ma J,Zou Z,Jemal A.Cancer statistics,2014.CA Cancer J Clin.2014.64(1):9-29.
[2]Cain JW,Hauptschein RS,Stewart JK,Bagci T,Sahagian GG,Jay DG.Identificationof CD44as a surface biomarker for drug resistance by surface proteome signature technology.Mol Cancer Res.2011.9(5):637-47.
[3]Bourguignon LY,Peyrollier K,Xia W,Gilad E.Hyaluronan-CD44interactionactivates stem cell marker Nanog,Stat-3-mediated MDR1gene expression,andankyrin-regulated multidrug efflux in breast and ovarian tumor cells.J Biol Chem.2008.283(25):17635-51.
[4]Bourguignon LY,Spevak CC,Wong G,Xia W,Gilad E.Hyaluronan-CD44interaction with protein kinase C(epsilon)promotes oncogenic signaling by the stem cellmarker Nanog and the Production of microRNA-21,leading to down-regulation of the tumorsuppressor protein PDCD4,anti-apoptosis,and chemotherapy resistance in breast tumor cells.J Biol Chem.2009.284(39):26533-46.
[5]Cheng Y,Tao L,Xu J,et al.CD44/cellular prion protein interact in multidrugresistant breast cancer cells and correlate with responses to neoadjuvant chemotherapy inbreast cancer patients.LID-10.1002/mc.22021[doi].Mol Carcinog.2013.。
[6]M.Yu,L.Zhou,J.Zhang,P.Yuan,P.Thorn,W.Gu,and C.Yu,A simple approach toprepare monodisperse mesoporous silica nanospheres with adjustable sizes.J.ColloidInterface Sci.376,67-75(2012).
[7]Wang X,Teng ZG,Huang XY,Lu GM.Mesoporous silica nanoparticles for cancertheranostic drug delivery.Yao Xue Xue Bao.2013.48(1):8-13.
Brief description of the drawings
Fig. 1 is for the electromicroscopic photograph of mesoporous silicon dioxide nano particle of administration.
Fig. 2 mesoporous silicon dioxide nano particle (MSN), amido modified mesoporous silicon dioxide nano particle (MSN-NH
2) and load Fourier's infrared spectrum spectrogram of the mesoporous silicon dioxide nano drug-supplying system (MSN-IM7) of monoclonal antibody IM7.
Fig. 3 is administration nano-drug administration system (MSN-IM7) and the growth inhibited effect of CD44 monoclonal antibody IM7 to drug resistance breast cancer cell of coupling CD44 monoclonal antibody relatively.A figure shows that drug resistance breast cancer cell line mcf-7/MDR1 has the drug resistance higher than parent breast cancer cell line mcf-7.B figure shows that the nanoparticle of preparation has good biocompatibility, faint to the toxicity of drug resistance breast cancer cell, plays the effect of carrying platform.The CD44 monoclonal antibody IM7 that C figure is more simple and coupling the cell growth inhibition of mesoporous silicon dioxide nano drug-supplying system (MSN-IM7) of CD44 monoclonal antibody IM7.
Fig. 4 comparative control group (Control), amycin group (DOX), the administration nano-drug administration system group (DMSN) of only loading amycin and coupling IM7 the administration nano-drug administration system group (DMSN-IM7) of loading amycin after treatment nude mice drug resistance transplanted tumor, the fluorescence intensity comparison of four groups of tumor biopsies.
Fig. 5 comparative control group (Control), amycin group (DOX), the administration nano-drug administration system group (DMSN) of only loading amycin and coupling IM7 administration nano-drug administration system group (DMSN-IM7) group of loading amycin after treatment nude mice drug resistance transplanted tumor, the comparison of the apoptotic cell of four groups of transplanted tumor sections.
Detailed description of the invention
According to following embodiment, the present invention may be better understood.But, those skilled in the art will readily understand, the described content of embodiment is only for the present invention is described, and should also can not limit the present invention described in detail in claims.
Embodiment 1: the preparation of medicine-carried nano particles.
Adopting hexadecyltrimethylammonium chloride (CTAC) is surfactant, utilizes template in the mixed phase of second sodium acetate and water, to prepare mesoporous silicon dioxide nano particle.Be specially first 6.24g hexadecyltrimethylammonium chloride is dissolved in to 0.3g NaAc3H
2in the mixed liquor of O and 53.4g water, at 60 DEG C, stir 2h, dropwise add the positive silicic acid second vinegar of 4.35mL.Continue 400RPM at 60 DEG C and stir 24h.Then remove supernatant at the centrifugal 10min of 20,000RPM, clean after 3 times, calcining sample 5h at 650 DEG C.The sub-form rule of mesoporous silicon dioxide nano particle obtaining, the about 60nm of particle diameter.
Nano material has been prepared the rear transmission electron microscope that utilizes the nano SiO 2 particle of preparation has been characterized: granule is suspended in appropriate water, in ultrasound wave, ultrasonic 1min fully disperses granule, then by it on formal film copper mesh, after natural drying, take pictures with transmission electron microscope, the results are shown in Figure the big or small homogeneous of mesoporous silicon dioxide nano particle in 1, figure, the about 60nm of size, favorable dispersibility, surface has meso-hole structure.
Embodiment 2: build the administration nano-drug administration system that loads CD44 monoclonal antibody IM7.
1) first adopt 3-aminopropyl triethoxysilane (APTES) to carry out amido modified to mesoporous silicon dioxide nano particle sub-surface, utilize Fourier's infrared spectrum analysis to characterize it, detect the amino group whether being connected with on nanoparticle.Concrete operations are: in 100ml dehydrated alcohol reaction system, in ultrasound wave, ultrasonic 2-5min fully disperses granule, add 1-2ml APTES room temperature 400RPM to stir after 24h, and with the centrifugal 5min of 13000rpm speed, vacuum drying is for subsequent use.Fourier's infrared spectrum spectrogram is shown in have-NH2 of the MSN-MH2 of accompanying drawing 2 group (3463.6nm place, peak).
2) on this basis, utilize 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxy-succinamide (EDC/NHS) activation system by the activated carboxylic on CD44 monoclonal antibody IM7, then carry out being connected of antibody I M7 with amido modified mesoporous silicon dioxide nano particle by condensation reaction, recycling Fourier infrared spectrum analysis characterizes it, detects on nanoparticle CD44 monoclonal antibody IM7 in whether coupling.Concrete operations are: get 0.1-1mg EDC, and 0.3-3mg NHS, stirring and dissolving in the 0.1M2-of 1ml morpholino b acid MES solution, adds 20-50 μ g people source CD44 antibody I M7, and room temperature magnetic agitation stirs the carboxyl of 15min activation antibody; To in 10ml phosphate buffer reaction system, add antibody and 5-10mg mesoporous silicon dioxide nano particle of activation again, cessation reaction after room temperature magnetic agitation 2h, with 13000rpm speed, centrifugal 5min abandons supernatant; Finally, add amycin 1-2mg lucifuge magnetic agitation 24h in phosphate buffer 5-10ml reaction system, with 13000rpm speed, centrifugal 5min abandons supernatant, and phosphate buffer cleans.Fourier's infrared spectrum spectrogram see on the MSN-IM7 of accompanying drawing 2, have antibody carbonyl group (peak 1377.2,1458nm place) and-CH (peak 2959.8,2923.7nm place), thereby verified that the structure of the administration nano-drug administration system of coupling CD44 monoclonal antibody is effective
3) mesoporous silicon dioxide nano particle sub-surface has silanol key, electronegative; Chemotherapeutics amycin has hydroxyl, amido, quinonyl, positively charged, therefore can utilize the electrostatic interaction and the hydrogen bonding effect that exist between mesoporous silicon dioxide nano material of main part and guest molecule amycin to carry out medicine carrying.Medicine carrying process is avoided the violent condition such as high temperature or strong acid and strong base, guarantees that the antibody having connected keeps active.Adopt the solution supernatant after UV spectrophotometer measuring medicine carrying, calculate medicine carrying and measure 8.9%, complete coupling CD44 monoclonal antibody IM7 and carry altogether the structure of the administration nano-drug administration system of chemotherapeutics.
Embodiment 3: relatively MSN-IM7 and the growth inhibited effect of IM7 to drug resistance breast cancer cell.
Cytotoxicity experiment can Check processing after the variation of drug-resistant tumor cells survival rate.First parent's breast carcinoma cell strain and its drug resistance breast carcinoma cell strain are carried out to cytotoxicity experiment, checking subject cell strain MCF-7/MDR1 is drug resistance breast carcinoma born of the same parents strains; Then simple nanoparticle is carried out to cytotoxicity experiment, illustrate that nanoparticle itself is nontoxic, the cytotoxicity of administration nano-drug administration system is the drug release coming from drug-supplying system; Finally, relatively MSN-IM7 and the growth inhibited effect of IM7 to drug resistance breast cancer cell, illustrate taking nanoparticle as carrying platform, obviously strengthened the growth inhibited effect of CD44 monoclonal antibody IM7 to drug resistance breast cancer cell.
Impact with sulfo group rhodamine B (SRB) method detection of drugs on human breast carcinoma mdr cell MCF-7 or MCF-7/MDR1 growing multiplication.The trophophase tumor cell of taking the logarithm, is inoculated in 96 well plates, and cell number is 5 × 10
3/ hole, at 37 DEG C, 5%CO
2in incubator, cultivate after 12 hours, grouping dosing, each concentration is set up parallel hole, and negative control hole adds normal saline, after 48 hours, every hole adds 4 DEG C of fixing 1h of 10% trichloroacetic acid, then adds SRB dyeing 15m in, and acetic acid washing is dried for 5 times, Tris dissolves, and surveys every hole optical density (OD) value under 515nm.Result has the drug resistance higher than parent breast cancer cell line mcf-7 as accompanying drawing 3:A figure shows drug resistance breast cancer cell line mcf-7/MDR1.B figure shows that the nanoparticle MSN of preparation has good biocompatibility, even in the time of high concentration 1000 μ g/ml, substantially nontoxic to drug resistance breast cancer cell, is good carrying platform.The cell growth inhibition of the mesoporous silicon dioxide nano drug-supplying system (MSN-IM7) of the C more simple IM7 of figure and coupling IM7, cytotoxicity experiment shows that MSN-IM7 has strengthened the inhibitory action of IM7 to drug resistance breast cancer cell.When containing IM7 concentration, the MSN-IM7 while being 2 μ g/ml can make drug resistance breast cancer cell vigor be down to 74.1%, and simple IM7 concentration is while reaching 15 μ g/ml, just can make drug resistance breast cancer cell vigor be down to 71.7%.With blank comparison,
#p<0.05.Therefore, antibody I M7 has the growth inhibited effect to drug resistance breast cancer cell; And taking nanoparticle as carrying platform to load upper CD44 monoclonal antibody IM7, can further strengthen the inhibitory action of IM7.
Embodiment 4: comparative control group (Control), amycin group (DOX), the administration nano-drug administration system group (DMSN) of only loading amycin and coupling IM7 also load the effect of administration nano-drug administration system group (DMSN-IM7) the treatment nude mice drug resistance transplanted tumor of amycin.
The Nude Mouse Model of model human breast carcinoma drug-resistant cell strain MCF-7/MDR1, is then divided into matched group (Control), amycin (DOX) administration group, mesoporous silicon dioxide nano drug-supplying system (DMSN) the administration group of loading amycin and targeting CD44 and overcomes mesoporous silicon dioxide nano drug-supplying system (DMSN-IM7) the administration group of tumor drug resistance at random.Matched group gives normal saline, other three groups intratumor injection amycin, the DMSN that contains equivalent amycin or DMSN-IM7 respectively.Adopt fluorescence imaging system to obtain the fluoroscopic image of breast carcinoma drug resistance transplanted tumor section under different treatment conditions.Detect the fluorescence intensity of amycin by Image Pro Express system, respectively organize the content of amycin in drug-resistant tumor.Amycin amount in the tumor tissue section of result demonstration DMSN-IM7 administration group is many and widely distributed, and the fluorescence of DOX group is distributed in tumor interstitial around more, and the fluorescence of DMSN group has part distribution in tumor epithelial cell.Description of test due to administration nano-drug administration system DMSN-IM7 coupling IM7, the directly drug resistance breast cancer cell of targeting high expressed CD44, make amycin hold-up in drug-resistant tumor tissue increase and distribute wide, see accompanying drawing 4, there is the feature of autofluorescence according to amycin, the relatively fluorescence intensity of amycin, compares the hold-up of amycin in drug resistance breast cancer transplantable tumor tissue.Adopt fluorescence imaging system to obtain the fluoroscopic image of breast carcinoma drug resistance transplanted tumor section under four groups of different treatment conditions.In figure, show that the fluorescence intensity of DMSN-IM7 group is the strongest and it is the most extensive in transplanted tumor, to distribute, illustrate that administration nano-drug administration system DMSN-IM7 obviously increases the hold-up of amycin in drug resistance transplanted tumor.
Breach end-labelling (TUNEL) with the mediation of deoxyribonucleotide terminal transferase detects apoptosis situation in four groups of drug-resistant tumor tissues, the drug-resistant tumor cell that result is presented at apoptosis in the tumor tissue section of DMSN-IM7 administration group under 400 times of light microscopics is maximum, the shrinkage of sepia karyon, dense dying.This is consistent in the maximum results of tumor intensive amount with the amycin of DMSN-IM7 administration group.Description of test is the strongest by the effect of DMSN-IM7 induction breast carcinoma mdr cell apoptosis, sees accompanying drawing 5.
The above is optimization embodiment of the present invention, not in order to restriction invention, all any amendments of doing within the spirit and principles in the present invention, is equal to and replaces and improvement etc., within all should being included in protection scope of the present invention.
Claims (10)
1. an administration nano-drug administration system that suppresses multidrug resistance growth of breast cancers, is characterized in that, it loads chemotherapeutics and CD44 monoclonal antibody taking monodispersed mesoporous silicon dioxide nano particle as carrier simultaneously.
2. the administration nano-drug administration system of inhibition multidrug resistance growth of breast cancers according to claim 1, is characterized in that, described monodispersed mesoporous silicon dioxide nano particle seed footpath is 20-100nm, and pattern is spherical, oval or cylindrical.
3. the administration nano-drug administration system of inhibition multidrug resistance growth of breast cancers according to claim 1, is characterized in that, described chemotherapeutics is mammary cancer chemotherapy medicine.
4. the administration nano-drug administration system of inhibition multidrug resistance growth of breast cancers according to claim 3, is characterized in that, described chemotherapeutics is any one or a few the combination in amycin, paclitaxel and cisplatin.
5. the administration nano-drug administration system of inhibition multidrug resistance growth of breast cancers according to claim 1, is characterized in that, described CD44 monoclonal antibody is CD44 monoclonal antibody IM7.
6. the preparation method of the administration nano-drug administration system of inhibition multidrug resistance growth of breast cancers claimed in claim 1, is characterized in that, the method comprises the steps:
(1) monodispersed mesoporous silicon dioxide nano particle of preparation or purchase, particle diameter is 20-100nm, pattern is spherical, oval or cylindrical;
(2) mesoporous silicon dioxide nano particle sub-surface step (1) being obtained carries out amino or carboxyl functional group is modified;
(3) mesoporous silicon dioxide nano particle after step (2) is modified carries out the loading of CD44 monoclonal antibody, the administration nano-drug administration system of preparation coupling CD44 monoclonal antibody;
(4) administration nano-drug administration system of coupling CD44 monoclonal antibody step (3) being obtained loads chemotherapeutics, prepares the administration nano-drug administration system that suppresses multidrug resistance growth of breast cancers.
7. the preparation method of the administration nano-drug administration system of inhibition multidrug resistance growth of breast cancers according to claim 6, it is characterized in that, in step (2), adopt 3-aminopropyl triethoxysilane to carry out mesoporous silicon dioxide nano particle sub-surface amido modified, or adopt glutaric anhydride to carry out carboxyl modified to mesoporous silicon dioxide nano particle sub-surface.
8. the preparation method of the administration nano-drug administration system of inhibition multidrug resistance growth of breast cancers according to claim 7, it is characterized in that, in step (3), utilize 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxy-succinamide activation system by the activated carboxylic on CD44 monoclonal antibody IM7, then carry out being connected of antibody I M7 with amido modified mesoporous silicon dioxide nano particle by condensation reaction; Or utilize 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxy-succinamide activation system by the mesoporous silicon dioxide nano particle activation of carboxyl modified, then carry out being connected of antibody I M7 with the amino on CD44 monoclonal antibody IM7 by condensation reaction.
9. the preparation method of the administration nano-drug administration system of inhibition multidrug resistance growth of breast cancers according to claim 8, it is characterized in that, in step (4), utilize the electrostatic interaction and the hydrogen bonding effect that between the administration nano-drug administration system of coupling CD44 monoclonal antibody and chemotherapeutics, exist to carry out medicine carrying.
10. the administration nano-drug administration system of inhibition multidrug resistance growth of breast cancers claimed in claim 1 suppresses the application in multidrug resistance breast cancer cell growth medicine in preparation.
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|---|---|---|---|---|
| CN107683142A (en) * | 2015-04-02 | 2018-02-09 | 卫理公会医院 | The method of cancer vaccine and enhancing antineoplastic immune based on porous silicon particulate |
| CN108671236A (en) * | 2018-05-07 | 2018-10-19 | 马鞍山市人民医院 | Special target breast cancer cell nanometer drug-loading system and preparation method thereof |
| CN110960508A (en) * | 2019-11-13 | 2020-04-07 | 湖北大学 | Starch nano-particle with protein adsorption resistance and targeting capability and preparation method thereof |
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| WO2011130753A2 (en) * | 2010-04-14 | 2011-10-20 | The University Of Washington Through Its Center For Commercialization | Functionalized nano- and micro-materials for medical therapies |
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| WO2011130753A2 (en) * | 2010-04-14 | 2011-10-20 | The University Of Washington Through Its Center For Commercialization | Functionalized nano- and micro-materials for medical therapies |
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| FENG CHEN等: "In vivo tumor targeting and image-guided drug delivery with antibody-conjugated, radiolabeled mesoporous silica nanoparticles", 《ACS NANO. AUTHOR MANUSCRIPT》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107683142A (en) * | 2015-04-02 | 2018-02-09 | 卫理公会医院 | The method of cancer vaccine and enhancing antineoplastic immune based on porous silicon particulate |
| CN108671236A (en) * | 2018-05-07 | 2018-10-19 | 马鞍山市人民医院 | Special target breast cancer cell nanometer drug-loading system and preparation method thereof |
| CN110960508A (en) * | 2019-11-13 | 2020-04-07 | 湖北大学 | Starch nano-particle with protein adsorption resistance and targeting capability and preparation method thereof |
| CN110960508B (en) * | 2019-11-13 | 2021-11-23 | 湖北大学 | Starch nano-particle with protein adsorption resistance and targeting capability and preparation method thereof |
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