CN104368000A - Targeting modified gold nanorod targeted drug delivery compound and application of delivery compound to anti-tumor photothermal therapy - Google Patents
Targeting modified gold nanorod targeted drug delivery compound and application of delivery compound to anti-tumor photothermal therapy Download PDFInfo
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Abstract
The invention relates to a targeting modified gold nanorod targeted drug delivery compound and an application of the delivery compound to anti-tumor photothermal therapy. The delivery compound is characterized in that a two-layer lipidosome structure similar to a cell membrane structure is formed by temperature-sensitive macromolecule K3, temperature-sensitive macromolecule 09JA, lecithin and Mal-PEG-DSPE; medicines and gold nanorods are packed into the lipidosome; target molecules are modified on the surface of the lipidosome. The invention also provides a preparation method and an application of the delivery compound. The targeting modified gold nanorod targeted drug delivery compound has the advantages that the release of the drugs such as adriacin doxorubicin can be effectively controlled by virtue of photo-thermal characteristics of gold nanorods and unique physicochemical property of temperature-sensitive lipidosome; by virtue of specific antigen-antibody binding effect, drug-carrying nanoparticles target tumor (such as breast cancer) cells; compared with free drug, the nano drug-carrying system is relatively long in half-life period and obvious in photothermal tumor inhibitory effect, and can be used for remarkably improving the bioavailability of the drugs.
Description
Technical field
The present invention relates to technical field of pharmaceuticals, specifically, is that the nanometer gold bar targeted drug of targeting modification is passed and released complex and the application of antitumor photo-thermal therapy thereof.
Background technology
Malignant tumor (cancer) is the second largest disease of serious threat human health, its cure rate is low and mortality rate is high, according to World Health Organization's whole world cancer report display, be close on 2008 and have 760 to die ten thousand deaths in 1,200 ten thousand cancer patients to die, the death that cancer causes accounts for about 13% of total death toll in the whole world.China's cancer incidence is in the quick rising stage at present, in China, and annual pathogenesis of cancer number about 2,600,000, dead nearly 1,800,000 people.The reasons such as viral infection (Epstein-Barr virus, hepatitis B virus and human papillomavirus), bacteriological infection (helicobacter pylori), carcinogen, ultraviolet radiation (UV) and gene mutation all may cause cancer.In China, breast carcinoma, as current cancer occurred frequently, is occur in breast glandular epithelium tissue and have a strong impact on one of even life-threatening modal malignant tumor.Although conventional treatments such as radiotherapy, chemotherapy and the operative treatment adopted alleviates slight illness to a great extent clinically at present, all there is significant limitation in these methods, and late period, the rate of transform was high, and how not good more, its curative effect is difficult to further raising.Therefore, new Therapeutic Method becomes clinical cancer and prevents and treats the important topic faced.
The nearly more than ten years, utilize the carrier loaded chemotherapeutics of function nano, while minimizing medicine is to non-target spot position toxic and side effects, reduces Drug therapy dosage as far as possible and reduce administration number of times, thus improving curative effect of medication, for clinical therapy of tumor brings new hope.Compared with traditional pharmaceutical carrier, nano-medicament carrier has following advantage: stable in body, non-immunogenicity, can realize the controllable release of medicine or gene, effectively extend action time, improves, maintains drug level, improve bioavailability.
Nanometer gold bar (Gold nanorods, GNRs) has good optical characteristics, has higher plasma resonance intensity under very narrow spectral bandwidth, in tumor photo-thermal treatment, have stronger photothermal conversion advantage than other metal materials.
Result of study shows, nanometer gold bar self has very strong photothermal conversion effect (temperature can raise 5-10 DEG C rapidly in the short period of time under specific optical maser wavelength stimulates), and its photo-thermal effect of the nanometer gold bar of different draw ratio also has difference (main cause of photo-thermal effect is that nanometer gold bar is understood because polarization is heat energy light energy conversion under the laser of specific wavelength irradiates), simultaneously this research also find nanometer gold bar self have selective killing effect to tumor cell (to tumor cell kill and wound intensity compare intensity height about 15% is killed and wounded to ordinary cells).In traditional clinical medicine chemotherapy, how to reduce the toxic and side effects of medicine and to improve enrichment in the drug loading of carrier and tumor be our present urgent need to solve the problem, therefore we synthesize and prepare the complex carrier that nanometer gold bar is combined with chemotherapeutics.Nanometer gold bar and chemotherapeutics wrap up by the temperature sensitive macromolecule using us to synthesize, under specific excitation wavelength stimulates, light energy conversion is heat energy by nanometer gold bar, the rising of temperature makes temperature sensitive macromolecule change from hydrophilic to hydrophobicity, its form is collapsed gradually, thus by the amycin release in temperature sensitive for trapping gold nanometer rods liposome.On this basis, we have also carried out finishing to the complex carrier of nanometer gold bar combination medicine, connect HER-2 antibody that sulfhydrylation modifies to be used for targeting targetedly on its surface there is the tumor cell of high expressed HER-2 antigen, thus enhance the toxic and side effects further reducing medicine normal tissue for targeting of the tumor cell of nanometer gold bar medicine complex carrier.
Summary of the invention
The object of the invention is for deficiency of the prior art, provide a kind of photo-thermal tumor suppression targeted drug to pass and release complex.
Of the present invention again one object be provide a kind of photo-thermal tumor suppression targeted drug to pass the preparation method releasing complex.
Another object of the present invention provides a kind of photo-thermal tumor suppression targeted drug to pass the application releasing complex.
For achieving the above object, the technical scheme that the present invention takes is: a kind of photo-thermal tumor suppression targeted drug is passed and released complex, complex is formed similar membrane structure lipid bilayer body structure by temperature sensitive macromolecule, lecithin and bridging agent is released in described passing, medicine and nanometer gold bar are wrapped up in described liposome, and modifies targeted molecular at described surface of liposome.
Described liposome is the bilayer liposomes forming similar membrane structure with temperature sensitive macromolecule K3, temperature sensitive macromolecule 09JA, lecithin, Mal-PEG-DSPE.Described lecithin is lecithin PC.
Described targeted molecular is monoclonal antibody anti-Her2-Fab.
Described pass that to release complex be prepared by following method: temperature sensitive macromolecule K3, temperature sensitive macromolecule 09JA, lecithin and Mal-PEG-DSPE make film by the method for revolving steaming, the blended liquid of nanometer gold bar and amycin being carried out resuspended to revolving the lipid macromolecule binding film being steamed into film, forming the carrier complexes of parcel nanometer gold bar and amycin; By the targeted molecular of the maleic groups link sulfhydrylation of surface of liposome.
Described pass that to release complex be that following method prepares: get temperature sensitive macromolecule K3, macromolecule 09JA, lecithin and Mal-PEG-DSPE and be dissolved in the methanol that volume ratio is 1:1 respectively: in chloroformic solution, solution blending putting into revolves and steams bottle and be filled with N
2carry out revolving steaming, rotating speed is 50r/min, rotary evaporation film forming; Utilize amycin and the blended aqueous solution of nanometer gold bar to carry out eluting to thin film, eluate utilizes the dialyzer of 3500 units to dialyse; The anti-Her-Fab that solution after dialysis is good with sulfhydrylation is connected, and anti-Her2-Fab:Mal-PEG-DSPE mol ratio is 1:10.
For realizing above-mentioned second object, the technical scheme that the present invention takes is: a kind of photo-thermal tumor suppression targeted drug passs the preparation method releasing complex, described preparation method comprises the following steps: get temperature sensitive macromolecule K3, macromolecule 09JA, lecithin and Mal-PEG-DSPE and be dissolved in the methanol that volume ratio is 1:1 respectively: in chloroformic solution, and solution blending putting into revolves and steams bottle and be filled with N
2carry out revolving steaming, rotating speed is 50r/min, rotary evaporation film forming; Utilize amycin and the blended aqueous solution of nanometer gold bar to carry out eluting to thin film, eluate utilizes the dialyzer of 3500 units to dialyse; The anti-Her-Fab that solution after dialysis is good with sulfhydrylation is connected, and anti-Her2-Fab:Mal-PEG-DSPE mol ratio is 1:10.
For realizing above-mentioned 3rd object, the technical scheme that the present invention takes is: the application of complex in the medicine preparing Therapeutic cancer is released in described passing.
Described cancer is breast carcinoma.
The invention has the advantages that:
The present invention utilizes nanometer gold bar (Gold nanorods, the physics and chemistry character of this uniqueness of optics fast temperature response GNRs), nanometer gold bar and hydrophobic chemotherapeutic drugs Doxorubicin etc. (DOX) are wrapped up in temperature sensitive liposome, under specific excitation wavelength stimulates, light energy conversion is heat energy by nanometer gold bar, the rising of temperature makes temperature sensitive macromolecule change from hydrophilic to hydrophobicity, its form is collapsed gradually, thus by the amycin release in temperature sensitive for trapping gold nanometer rods liposome, connect the targeted molecular such as antibody that sulfhydrylation modifies to be used for targeting targetedly on its surface there is the tumor cell of high expressed antigen, thus the tumor cell enhancing nanometer gold bar medicine complex carrier is for targeting, the toxic and side effects of further minimizing medicine normal tissue.Found that the excellent medicine complex carrier of two targeted nano gold has obvious photo-thermal tumor-inhibiting action, provide useful reference to clinical antineoplastic treatment.
Accompanying drawing explanation
Accompanying drawing 1 is the particle diameter that nanometer gold bar surveyed by Dynamic laser scattering instrument.
Accompanying drawing 2 is the Apparent character observing nanometer gold bar under transmission electron microscope.
Accompanying drawing 3 is structure schematic diagrams of the excellent complex carrier of two targeted nano gold.
Accompanying drawing 4 is droplet measurement of the excellent complex carrier of two targeted nano gold.
Accompanying drawing 5 is the excellent complex carrier TEM somatometry of physique of two targeted nano gold.
Accompanying drawing 6 is that the cytotoxicity of the excellent complex carrier of two targeted nano gold detects.
Accompanying drawing 7 is that inverted fluorescence microscope observes the excellent carrier cell endocytosis of two targeted nano gold.
Accompanying drawing 8 is MCF-7 human breast cancer cell tumor bearing nude mice drug injection gross tumor volume measurement results.
Detailed description of the invention
Below in conjunction with accompanying drawing, detailed description of the invention provided by the invention is elaborated.
The breast carcinoma targeted drug that the object of the present invention is to provide a kind of antibody target to modify pass release complex with and preparation method thereof, and its Tumor suppression effect to be studied.
The present invention is with temperature sensitive macromolecule K3 and 09JA, and lecithin, Mal-PEG-DSPE is stock, prepares a kind of target drug-carrying system can carrying water soluble drug amycin and nanometer gold bar.
Targeted nano carrier system prepared by the present invention has following features:
(1) this carrier is with temperature sensitive macromolecule K3 and 09JA, lecithin, Mal-PEG-DSPE is the lipid bilayer body structure that stock forms similar membrane structure, by the interaction in liposome between hydrophilic component and water soluble drug, medicine, nanometer gold bar are wrapped up in liposome, forms the medicine-carried system of nano-scale;
(2) by the active group on nano-carrier surface, monoclonal antibody anti-Her2-Fab is connected to nano-carrier surface, by antigen-antibody specific bond effect, makes medicine-carried nano particles targeting breast cancer cell; Described nanometer medicine-carried system has the longer half-life compared with free drug, can significantly improve the bioavailability of medicine.
The preparation method of temperature sensitive macromolecule K3, temperature sensitive macromolecule 09JA please refer to: Li W, Zhao H., QianW, et al.Chemotherapy for gastric cancer by finely tailoring anti-Her2 anchoreddual targeting immunomicelles Biomaterials, 2012,33:5349.Mal-PEG-DSPE and bridging agent maleimide polyethylene glycol DSPE.
Embodiment 1
The configuration of seed liquor: CTAB (cetyl trimethyl ammonium bromide) the solution 5ml preparing 0.2M with MilliQ-water, the HAuCl of preparation 0.0005M
4solution 5ml.Above-mentioned CTAB solution is added HAuCl
4in solution, and slowly stir.The NaBH of preparation 0.01M ice
4solution 0.6ml, MilliQ-water prepare.By the NaBH configured
4solution slowly adds HAuCl
4in solution, find HAuCl
4solution is variable color gradually.Under the condition of room temperature, be positioned over magnetic stirring apparatus vigorous stirring 2min, in 25 DEG C of preservations after having stirred, the color of seed liquor has become dark brown.The configuration of growth-promoting media: the CTAB of the 0.2M of the 5ml prepared, is added the 0.004M AgNO of 0.15ml
3in solution (under 25 DEG C of conditions).The HAuCl of preparation 0.001M
4solution 5ml, adds the above-mentioned HAuCl prepared in the growth-promoting media prepared
4solution.The ascorbic acid (MilliQ-water preparation) of the 0.0788M of 75 μ L is added after slow stirring.In above-mentioned solution, add the gold seeds liquid (at 27-30 DEG C) of 12 μ L again and slowly stir.Solution colour changes gradually, and the colourless aubergine that becomes is normal, measures, obtain nanometer gold bar after at room temperature slowly stirring 10-20h to it.After the centrifugal 5min of nanometer gold bar sample centrifuge 8000r/min that taking-up prepares, with MilliQ-water, by vortex instrument wraps correction, it carries out resuspended, and the nanometer gold bar solution liquid nitrogen after resuspended carries out freezing freezing.Freeze dryer sets, and freeze temperature is-50 DEG C, carries out pre-cooling in advance to freeze dryer.Put into freeze dryer precooled in advance to the nanometer gold bar solution after freezing freezing and carry out lyophilizing, the nanometer gold bar powder taken out after the lyophilizing in lyophilizing bottle weighs.Re-start standardize solution with MilliQ-water to nanometer gold bar powder, demarcating its concentration is 0.6mg/ml.Filter the Millipore filter of the good nanometer gold bar solution of standardize solution with 0.45 μm, measure the nanometer gold bar sample filtered, measuring condition is: 90 ° of angle of scatterings, 25 DEG C.
Embodiment 2
Get and the nanometer gold bar sample solution after original solution dilutes 20 times is dripped (cover copper mesh and form droplet) on copper mesh, the copper mesh dripped after sample is put into fume hood and carries out drying, observation and analysis is carried out to the sample after process.
Embodiment 3
Take macromolecule K3 and each 0.5mg of macromolecule 09JA and be dissolved in methanol: in the solution of chloroform=1:1, making its cumulative volume be 2ml.Take Mal-PEG-DSPE 0.25mg and be dissolved in methanol: in the solution of chloroform=1:1, making its volume be 0.5ml.Take lecithin PC 2mg and be dissolved in methanol: in the solution of chloroform=1:1, making its cumulative volume be 2ml.These three kinds of solution blendings prepared are put into 50ml and are revolved and steam bottle and be filled with N2 and carry out revolving steamings (rotating speed is 50r/min), rotary evaporation until solution revolve form thin film bottom steaming bottle after take out.Preparation 2mg/ml DOX solution (solvent is pbs solution) is carried out blended with nanometer gold bar (numbering 150) solution of 1mg/ml.Get DOX and nanometer gold bar blended liquid 3ml to revolve be steamed into film after revolve and steam bottle and carry out eluting (attention lucifuge).After eluting solution lucifuge dialyse, dialyzer is the dialyzer of unit of SPECTRUM company 3500 of the U.S., and analysing liquid is MilliQ-water.Get the anti-Her-Fab good with sulfhydrylation of the solution after dialysis to carry out being connected (anti-Her2-Fab:Mal-PEG-DSPE mol ratio is 1:10), this group is as targeting group; Solution after a part being dialysed in addition is connected with the BSA of sulfhydrylation, is set to non-targeted group.Incubated at room temperature 2h (shaking table slight wobble).Dialysed by the solution be connected, dialyzer is 100KD, in 4 DEG C in pbs solution.
Embodiment 4
Take out the excellent complex carrier sample liquid nitrogen of two targeted nano gold prepared and carry out freezing freezing.Freeze dryer sets, and freeze temperature is-50 DEG C, carries out pre-cooling in advance to freeze dryer.The excellent complex carrier sample of two targeted nano gold after freezing freezing is put into freeze dryer precooled in advance and carries out lyophilizing.The powder taking out the excellent complex carrier sample of two targeted nano gold after the lyophilizing in lyophilizing bottle weighs.Re-start standardize solution with the powder of MilliQ-water to the excellent complex carrier sample of two targeted nano gold, demarcating its concentration is 0.5mg/ml.The Millipore filter of the good nanometer gold bar solution of standardize solution with 0.45 μm is filtered.Measure the nanometer gold bar sample filtered, measuring condition is: 90 ° of angle of scatterings, 25 DEG C.
Embodiment 5
Get being put on copper mesh after to the solution dilution 20 times of the excellent complex carrier of two targeted nano gold to drip (solution forms droplet on copper mesh).Dye to the copper mesh of sample after dropping, stain is phosphotungstic acid (Sodium phosphotungstate).The copper mesh dripped after sample is put into fume hood and carries out drying.Observation and analysis is carried out to the sample after process.
Embodiment 6
Plating cells: the human breast cancer cell line Bcap-37 cell pancreatin being in exponential phase is carried out digest, centrifugal after count again, every hole liquid-transfering gun inoculation 1.0 × 10 in 24 orifice plates
5cell, the volume of cell suspension is the cell culture fluid preparation of 200 μ L 10%FCS, is positioned over the CO2 of 7%, in the cell culture incubator of 37 DEG C, incubated overnight 12h.The golden excellent carrier (d-AuNR-BSA) of the targeted nano excellent carrier of gold (d-AuNR-Fab) getting parcel amycin respectively, the single targeted nano wrapping up amycin adds (wherein low concentration group nanometer gold bar concentration 0.5mg/ml doxorubicin concentration 5 μ g/ml high concentration group nanometer gold bar concentration 1mg/ml doxorubicin concentration 10 μ g/ml) in cell hole, hatch with MCF-7 cell, hatch 12h 37 DEG C and 42 DEG C respectively for each group.Above-mentioned 24 orifice plates added are carried out laser irradiation with the fixed band generating laser of French Venus company respectively, and (every hole irradiation time is 5min laser facula is 1cm
2lASER Light Source and cell plates between distance be 10cm, laser light source power is set as that 500mW wavelength is set as 808nm).Carry out laser illuminated after put into 7% CO2, in the cell culture incubator of 37 DEG C, carry out 12h incubated overnight.The cell plates of incubated overnight are first carried out to cleaning 1 time with pbs solution and then wash after 2 times gently with by culture medium, detection cells survival rate is carried out with Cell Counting Kit-8 test kit, testing conditions is: CCK-8 reagent every hole 20 μ l, hatches 2h for 37 DEG C.Detecting instrument condition is: BIO-TEK ELx800 full-automatic microplate reader in 450nm place reads absorbance.
Embodiment 7
Plating cells: the MCF-7 cell dissociation of trophophase of taking the logarithm, centrifugal rear counting is 2 × 10 at 24 orifice plate middle berth cell densities
5/ hole, every hole adds 500 μ l containing serum free culture system liquid, and the blanc cell hole that makes a circle in week is each all supplies with the PBS of 500 μ l, is placed on 7%CO2, spends the night in the cell culture incubator of 37 DEG C.Getting amycin, the targeted nano excellent carrier of gold (d-AuNR-Fab) of parcel amycin, the single targeted nano excellent carrier of gold (d-AuNR-BSA) of parcel amycin and carrier amycin group (d-adr) respectively adds in cell hole, hatch with N87 cell, hatch 6h 37 DEG C and 42 DEG C respectively for each group.After hatching 12h, d-AuNR-Fab group and d-AuNR-BSA group are washed 2 times (note cell keep adherent) gently by culture medium respectively, then the situation of observation of cell endocytosis under inverted fluorescence microscope.
Embodiment 8
The Balb/c nude mice being vaccinated with MCF-7 human breast cancer cell is carried out random packet, be grouped into 5 groups, comprise single targeted nano gold excellent complex carrier injection group, nanometer gold bar injection group after the excellent complex carrier injection group of two targeted nano gold after amycin matched group, pbs injection of solution matched group, parcel amycin, parcel amycin.Often organizing Balb/c nude mice is 5, on average the Balb/c nude mice rice time injection of every lotus tumor is 5mg/kg (the two targeted nano excellent complex carrier injection group of gold after parcel amycin and the excellent complex carrier injection group of single targeted nano gold after parcel amycin are the amount that acetonitrile breaks rear demarcation) according to the dosage of amycin, contained by the two targeted nanos excellent complex carrier injection group of gold after nanometer gold bar injection group concentration and parcel amycin and the golden excellent complex carrier injection group two groups of single targeted nano after wrap up amycin, nanometer gold bar concentration is for seek unity of standard, the injected dose of each nanometer gold bar is 2mg/kg.Inject 5 times, on average injection in every 3 days once (prevents the side effect of simple amycin injection group tumor bearing nude mice from causing nude mice death before not completing experiment).Start record when first day drug injection and observe at any time and record the Survival that often group is vaccinated with the lotus tumor Balb/c nude mice of MCF-7 human breast cancer cell, every 2 days measuring device tumor sizes also carry out weighing body weight to it.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the prerequisite not departing from the inventive method; can also make some improvement and supplement, these improve and supplement and also should be considered as protection scope of the present invention.
Claims (10)
1. a photo-thermal tumor suppression targeted drug is passed and is released complex, it is characterized in that, complex is formed similar membrane structure lipid bilayer body structure by temperature sensitive macromolecule, lecithin and bridging agent is released in described passing, medicine and nanometer gold bar are wrapped up in described liposome, and modifies targeted molecular at described surface of liposome.
2. according to claim 1 passing releases complex, it is characterized in that, described liposome is the bilayer liposomes forming similar membrane structure with temperature sensitive macromolecule K3, temperature sensitive macromolecule 09JA, lecithin, Mal-PEG-DSPE.
3. according to claim 1 passing releases complex, it is characterized in that, described medicine is amycin.
4. according to claim 1 passing releases complex, it is characterized in that, described lecithin is lecithin PC.
5. according to claim 1 passing releases complex, it is characterized in that, described targeted molecular is monoclonal antibody anti-Her2-Fab.
6. according to claim 1 passing releases complex, it is characterized in that, described pass that to release complex be that following method prepares: temperature sensitive macromolecule K3, temperature sensitive macromolecule 09JA, lecithin and Mal-PEG-DSPE make film by the method for revolving steaming, the blended liquid of nanometer gold bar and amycin being carried out resuspended to revolving the lipid macromolecule binding film being steamed into film, forming the carrier complexes of parcel nanometer gold bar and amycin; By the targeted molecular of the maleic groups link sulfhydrylation of surface of liposome.
7. according to claim 1 passing releases complex, it is characterized in that, described pass that to release complex be that following method prepares: get temperature sensitive macromolecule K3, macromolecule 09JA, lecithin and Mal-PEG-DSPE and be dissolved in the methanol that volume ratio is 1:1 respectively: in chloroformic solution, solution blending putting into revolves and steams bottle and be filled with N
2carry out revolving steaming, rotating speed is 50r/min, rotary evaporation film forming; Utilize amycin and the blended aqueous solution of nanometer gold bar to carry out eluting to thin film, eluate utilizes the dialyzer of 3500 units to dialyse; The anti-Her-Fab that solution after dialysis is good with sulfhydrylation is connected, and anti-Her2-Fab:Mal-PEG-DSPE mol ratio is 1:10.
8. according to claim 1ly pass the preparation method releasing complex, it is characterized in that, described preparation method comprises the following steps: get temperature sensitive macromolecule K3, macromolecule 09JA, lecithin and Mal-PEG-DSPE and be dissolved in the methanol that volume ratio is 1:1 respectively: in chloroformic solution, and solution blending putting into revolves and steams bottle and be filled with N
2carry out revolving steaming, rotating speed is 50r/min, rotary evaporation film forming; Utilize amycin and the blended aqueous solution of nanometer gold bar to carry out eluting to thin film, eluate utilizes the dialyzer of 3500 units to dialyse; The anti-Her-Fab that solution after dialysis is good with sulfhydrylation is connected, and anti-Her2-Fab:Mal-PEG-DSPE mol ratio is 1:10.
9. pass according to the arbitrary described medicine of claim 1-7 and release the application of complex in the medicine preparing Therapeutic cancer.
10. application according to claim 9, is characterized in that, described cancer is breast carcinoma.
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Cited By (7)
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| CN105078926A (en) * | 2015-08-26 | 2015-11-25 | 河南省医药科学研究院 | Nano-carrier entrapping anticancer drugs and gold nanoparticles lipids and preparation method of nano-carrier |
| CN106821986A (en) * | 2017-03-13 | 2017-06-13 | 浙江大学 | Gold nanorods lipid polymer vesica with percutaneous dosing function and its preparation method and application |
| CN107441507A (en) * | 2017-07-26 | 2017-12-08 | 苏州大学 | Diagnosis and treatment integration nano-probe and its application by tumour cell activation |
| CN108159432A (en) * | 2017-12-19 | 2018-06-15 | 华南师范大学 | A kind of targeted nano-particle for inhibiting breast cancer and its preparation and application |
| CN108273070A (en) * | 2018-02-11 | 2018-07-13 | 上海交通大学 | Cell and drug targeting exchanging structure and its preparation and application |
| CN113975248A (en) * | 2021-10-09 | 2022-01-28 | 广东省人民医院 | Tumor targeted diagnosis and treatment integrated nanoparticle and application thereof |
| CN115645546A (en) * | 2022-10-28 | 2023-01-31 | 中国药科大学 | Preparation and application of cell membrane modified adriamycin liposome |
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2014
- 2014-11-26 CN CN201410696584.0A patent/CN104368000A/en active Pending
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105078926A (en) * | 2015-08-26 | 2015-11-25 | 河南省医药科学研究院 | Nano-carrier entrapping anticancer drugs and gold nanoparticles lipids and preparation method of nano-carrier |
| CN106821986A (en) * | 2017-03-13 | 2017-06-13 | 浙江大学 | Gold nanorods lipid polymer vesica with percutaneous dosing function and its preparation method and application |
| CN106821986B (en) * | 2017-03-13 | 2020-02-07 | 浙江大学 | Gold nanorod-lipid polymer vesicle with transdermal drug delivery function and preparation method and application thereof |
| CN107441507A (en) * | 2017-07-26 | 2017-12-08 | 苏州大学 | Diagnosis and treatment integration nano-probe and its application by tumour cell activation |
| CN107441507B (en) * | 2017-07-26 | 2020-05-15 | 苏州大学 | Diagnosis and treatment integrated nanoprobe activated by tumor cells and application thereof |
| CN108159432A (en) * | 2017-12-19 | 2018-06-15 | 华南师范大学 | A kind of targeted nano-particle for inhibiting breast cancer and its preparation and application |
| CN108159432B (en) * | 2017-12-19 | 2020-12-15 | 华南师范大学 | Targeted nanoparticle for inhibiting breast cancer and preparation and application thereof |
| CN108273070A (en) * | 2018-02-11 | 2018-07-13 | 上海交通大学 | Cell and drug targeting exchanging structure and its preparation and application |
| CN108273070B (en) * | 2018-02-11 | 2020-10-16 | 上海交通大学 | Cell and drug targeting switching structure and preparation and application thereof |
| CN113975248A (en) * | 2021-10-09 | 2022-01-28 | 广东省人民医院 | Tumor targeted diagnosis and treatment integrated nanoparticle and application thereof |
| CN115645546A (en) * | 2022-10-28 | 2023-01-31 | 中国药科大学 | Preparation and application of cell membrane modified adriamycin liposome |
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