CN112057434A - Mesoporous silicon nano particle capable of responding X-ray medicine release and preparation method and application thereof - Google Patents
Mesoporous silicon nano particle capable of responding X-ray medicine release and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a mesoporous silicon nanoparticle capable of releasing medicine in response to X-rays, a preparation method and application thereof, and belongs to the technical field of medicine carriers. The preparation method of the mesoporous silicon nano particle capable of responding X-ray medicine release comprises the following steps: (1) preparing bis [3- (triethoxysilyl) propyl ] diselenide; (2) the preparation of the double-selenium mesoporous silicon nano particle capable of responding to X-ray medicine release. The diselenide mesoporous silicon prepared by the invention is the first mesoporous silicon capable of responding to X-ray to generate skeleton degradation. The invention takes bis [3- (triethoxysilyl) propyl ] diselenide and ethyl orthosilicate as a mixed silicon source, synthesizes the mesoporous silicon containing the double selenium bonds by a copolycondensation method, and the prepared double selenium mesoporous silicon can not only respond to X rays to quickly degrade and release drugs, but also respond to tumor redox microenvironment to slowly release drugs, thereby realizing the regulation and control of the drug degradation speed and the drug release speed.
Description
Technical Field
The invention belongs to the technical field of drug carriers, and particularly relates to mesoporous silicon nanoparticles capable of releasing drug in response to X-rays, and a preparation method and application thereof.
Background
Cancer has become a major disease threatening the life of people, chemotherapy is an effective treatment at present, but the quality of life of patients is reduced due to its serious toxic and side effects and poor prognosis effect. The progress of nanotechnology provides a new material and a new strategy for realizing efficient and safe tumor chemotherapy, and the nanometer material becomes a hotspot of tumor chemotherapy because of good tumor targeting and easy realization of combined treatment by multiple means, can improve the treatment efficiency and reduce side effects. The mesoporous silicon nano particle has the advantages of large specific surface area and pore volume, good biocompatibility, easy surface modification, capability of efficiently carrying various drugs, realization of controllable drug release and the like, and is expected to become an ideal drug carrier.
The mesoporous silicon carrier has wide application in tumor diagnosis and treatment, and the mesoporous silicon can realize environment-responsive drug release through a surface modification gating system or realize controllable degradation and drug release through a framework doped with organic elements. However, the problems of slow degradation, uncontrollable drug release and the like still exist at present, and further application of the compound is limited. The X-ray has the advantages of high penetration depth, no wound, easy realization of combined treatment with radiotherapy and the like in solid tumors, and is an exogenous stimulation factor suitable for controllable drug release of the mesoporous silicon at present. However, no research report on degradation of mesoporous silicon capable of responding to X-ray degradation and related drug release is found at present.
Disclosure of Invention
In order to overcome the defects of slow degradation and uncontrollable drug release of the existing mesoporous silicon, the invention aims to provide a preparation method of mesoporous silicon nanoparticles capable of responding to X-ray drug release.
The invention also aims to provide the mesoporous silicon nanoparticles capable of responding to X-ray drug release prepared by the preparation method and application thereof.
The invention further aims to provide a degradable mesoporous silicon nanoparticle drug delivery system and application thereof.
The purpose of the invention is realized by the following technical scheme:
a preparation method of mesoporous silicon nanoparticles capable of releasing drug in response to X-rays comprises the following steps:
(1) preparation of bis [3- (triethoxysilyl) propyl ] diselenide
Dripping gamma-chloropropyltrimethoxysilane into the sodium diselenide solution, stirring at room temperature overnight, stopping reaction, extracting, drying, and purifying the crude product by chromatography to obtain a dark yellow liquid, namely bis [3- (triethoxysilyl) propyl ] diselenide;
(2) preparation of double-selenium mesoporous silicon (MON) nanoparticles capable of releasing drug in response to X-ray
Dissolving a cation template agent and triethanolamine, heating and stirring; and then adding a mixed solution of tetraethoxysilane, bis [3- (triethoxysilyl) propyl ] diselenide and ethanol to obtain a system 1, continuously stirring, centrifugally collecting the nanoparticles, washing a solid crude product, refluxing the ammonium nitrate ethanol solution, centrifugally collecting, and drying to obtain the diselenide mesoporous silicon nanoparticles capable of responding to X-ray drug release.
The gamma-chloropropyltrimethoxysilane and the sodium diselenide in the step (1) are preferably calculated according to the molar ratio of 2: 1.
The room temperature in the step (1) is preferably 20-30 ℃.
The time of the overnight in the step (1) is preferably 8-12 hours.
The reaction stop described in step (1) is preferably stopped by adding ice water.
The organic solvent used in the extraction described in step (1) is preferably dichloromethane.
The drying described in the step (1) is preferably carried out by drying the organic layer with anhydrous sodium sulfate.
The chromatography in step (1) is preferably performed by silica gel column chromatography; the solvent for silica gel column chromatography is preferably Petroleum Ether (PE) and Dichloromethane (DCM) of 10-1: 1.
The cationic template described in step (2) preferably includes at least one of cetyltrimethyl-p-toluenesulfonyl ammonium (CTAT), cetyltrimethyl ammonium chloride (CTAC), and cetyltrimethyl ammonium bromide (CTAB).
The dosage of the cationic template agent in the step (2) is 0.3-15 wt% of the system 1; more preferably 1.5 wt%.
The dosage of the triethanolamine in the step (2) is 0.1-1.5 wt% of the system 1; more preferably 0.3 wt%.
The dissolved solvent in step (2) is preferably water; more preferably ultrapure water.
The heating temperature in the step (2) is preferably 40-90 ℃; more preferably 80 deg.c.
The stirring time in the step (2) is preferably 0.5-2 hours; more preferably 1 hour.
The rotating speed of stirring in the step (2) is preferably 400-1200 rpm; more preferably 900 rpm.
The using amount of the ethyl orthosilicate in the step (2) is 2-12 wt% of the system 1; more preferably 10 wt%.
The usage amount of the bis [3- (triethoxysilyl) propyl ] diselenide in the step (2) is 1-5 wt% of the system 1; more preferably 2.5 wt%.
The ethanol in the step (2) is preferably absolute ethanol; the amount of the absolute ethyl alcohol is 2.5-10 wt% of the system 1; more preferably 5 wt%.
The continuous stirring time in the step (2) is 1-10 hours; preferably 4 hours.
The washing in the step (2) is preferably washing with absolute ethyl alcohol; the number of washing is preferably at least three; more preferably three times.
The content of ammonium nitrate in the ammonium nitrate ethanol solution in the step (2) is 0-1 wt%.
The number of times of refluxing in the step (2) is preferably at least 3 times; more preferably three times.
Refluxing time in the step (2) is 6-48 hours per time; preferably 8-12 hours; more preferably 12 hours.
The drying in step (2) is preferably vacuum drying.
Mesoporous silicon nanoparticles capable of releasing drug in response to X-rays are prepared by the preparation method.
The dose of the responsive X-ray radiation of the mesoporous silicon nano particle capable of responding to the X-ray medicine release is preferably 0-10 Gy; more preferably 1 Gy.
The mesoporous silicon nano particle capable of responding to X-ray release is applied to the preparation of an anti-tumor drug delivery system.
A degradable mesoporous silicon nanoparticle drug delivery system comprises the mesoporous silicon nanoparticles capable of responding to X-ray drug release and a drug; the mesoporous silicon nano particle capable of responding to X-ray release is used as a carrier for loading the drug.
The drug preferably comprises, but is not limited to, a small molecule antitumor drug, and/or a derivative of a small molecule antitumor drug.
The small-molecule antitumor drug and/or the derivative of the small-molecule antitumor drug preferably comprises at least one of adriamycin, paclitaxel, docetaxel, vincristine sulfate, 5-fluorouracil, methotrexate, mitoxantrone, adenosine cyclophosphamide, perlomycin sulfate, carmine, iminoquinone, aclarubicin hydrochloride, carmustine, temozolomide, lomustine, carmofur, tegafur, actinomycin D, mitomycin, amsacrine, amifostine, cisplatin, ararelin, aminoglutethimide, mechlorethamine hydrochloride, sorafenib, nilotinib and dasatinib, and/or at least one derivative of the small-molecule antitumor drug.
The preparation method of the degradable mesoporous silicon nanoparticle drug delivery system comprises the following steps:
dissolving the medicine to prepare a medicine stock solution; under the ultrasonic condition, the mesoporous silicon nano particles capable of responding to X-ray release are dispersed into a drug stock solution to form a mixed solution; and (3) carrying out shake culture on the mixed solution, and centrifuging to obtain a solid, namely the double-selenium mesoporous silicon nanoparticle (MON @ DOX) loaded with the drug.
The solvent for dissolving the drug preferably includes at least one of water, glycerol, dimethyl sulfoxide (DMSO), Dimethylformamide (DMF), and isopropanol.
The concentration of the medicine in the medicine stock solution is preferably 0.1-20 mg/mL; more preferably 1 mg/mL.
The mass ratio of the drug to the mesoporous silicon nanoparticles capable of releasing drug in response to X-rays is preferably 1: 1-30; more preferably as 1: 1.
The shaking culture is preferably constant-temperature shaking; the oscillation conditions are preferably: carrying out shaking culture at the temperature of 37 ℃ and the rpm of 150-500 for 2-96 hours; more preferably: the temperature was 37 ℃ and shaking was carried out at 150rpm for 24 hours.
Drying the solid for later use; the drying is preferably vacuum drying; the temperature of the vacuum drying is preferably 0-40 ℃; more preferably 30 deg.c.
The degradable mesoporous silicon nano particle drug delivery system is applied to the preparation of drugs for treating cancers.
The treatment includes but is not limited to at least one of chemotherapy and chemotherapy-radiotherapy combination treatment.
Compared with the prior art, the invention has the following advantages and effects:
(1) the diselenide mesoporous silicon prepared by the invention is the first mesoporous silicon capable of responding to X-ray to generate skeleton degradation.
(2) The invention takes bis [3- (triethoxysilyl) propyl ] diselenide and ethyl orthosilicate as a mixed silicon source, synthesizes the mesoporous silicon containing the double selenium bonds by a copolycondensation method, and the prepared double selenium mesoporous silicon can not only respond to X rays to quickly degrade and release drugs, but also respond to tumor redox microenvironment to slowly release drugs, thereby realizing the regulation and control of the drug degradation speed and the drug release speed.
(3) According to the invention, the diselenide mesoporous silicon is synthesized by an improved sol-gel method, and the prepared degradable nano drug delivery system formed by loading the diselenide mesoporous silicon with the drug can realize efficient and safe chemotherapy and chemotherapy-radiotherapy synergistic treatment.
(4) The diselenide mesoporous silicon nano particles prepared by the method are used for loading micromolecular drugs, realize carrier degradation and drug controllable release responding to X-rays, and are used for efficient and safe tumor treatment.
(5) Different from the traditional mesoporous silicon, the preparation method of the mesoporous silicon nano particle capable of responding to X-ray drug release adopts the selenium-containing bis [3- (triethoxysilyl) propyl ] diselenide and the tetraethoxysilane as the mixed silicon source, and synthesizes the mesoporous silicon containing the double selenium bonds by a copolycondensation method, so that the mesoporous silicon containing the double selenium bonds can realize the carrier degradation and the drug release controllable by the X-ray, has better anti-tumor effect and simultaneously reduces the toxic and side effects, and is expected to become a new generation drug carrier for high-efficiency and safe tumor chemotherapy.
(6) The mesoporous silicon nano particles are double-selenium mesoporous silicon, can effectively support various chemotherapeutic drugs, can effectively prevent the drugs from leaking in the drug delivery process, can respectively respond to X rays and a redox microenvironment to generate skeleton degradation after reaching a tumor part, controllably releases the drugs, improves the anti-tumor effect, and simultaneously reduces the toxic and side effects of the drugs on normal cells/tissues. The mesoporous silicon nano particle prepared by the invention has the advantages of cheap and easily-obtained raw materials, obvious anti-tumor effect and good application prospect.
Drawings
FIG. 1 is a transmission electron microscope characterization result chart of the diselenide mesoporous silicon nanoparticles in example 1 of the present invention.
Fig. 2 is a graph showing the results of nitrogen adsorption and desorption curves of the diselenide mesoporous silicon nanoparticles in example 1 of the present invention.
FIG. 3 is a diagram of the results of transmission electron microscopy after X-ray irradiation and further incubation for 72 hours of the diselenide mesoporous silicon nanoparticles in example 2 of the present invention; wherein, the graph a shows the degradation condition of the diselenide mesoporous silicon nano particles after 1Gy X-ray irradiation; and the graph b shows the degradation condition of the diselenide mesoporous silicon nano particles after being irradiated by X rays and incubated for 72 hours.
FIG. 4 is a graph showing the results of the release of an doxorubicin drug in the drug loaded nano delivery system (MON @ DOX) made in example 3 of the present invention.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the present invention is not limited thereto.
In the present example, each reagent and raw material were commercially available unless otherwise specified.
Example 1: preparation of double-selenium mesoporous silicon (MON) nanoparticles capable of releasing drug in response to X-ray
A preparation method of mesoporous silicon nanoparticles capable of releasing drug in response to X-rays comprises the following steps:
(1) preparation of bis [3- (triethoxysilyl) propyl ] diselenide
Dropwise adding 10g of gamma-chloropropyltrimethoxysilane into 30mL of sodium diselenide solution (containing 0.0255mol of sodium diselenide), stirring at room temperature overnight, adding ice water to stop reaction, extracting dichloromethane, drying an organic layer by using anhydrous sodium sulfate, and purifying a crude product by silica gel column (300-400 meshes) chromatography (petroleum ether (PE) and Dichloromethane (DCM) are 10-1: 1) to obtain a deep yellow liquid, namely bis [3- (triethoxysilyl) propyl ] diselenide;
(2) preparation of double-selenium mesoporous silicon (MON) nanoparticles capable of releasing drug in response to X-ray
Taking 0.6g of cation template agent (hexadecyl trimethyl p-toluene ammonium sulfonate) and 0.15g of triethanolamine, adding 40mL of ultrapure water into a round-bottom flask, fully dissolving, heating to 80 ℃, and stirring for 1 hour; then adding a mixed solution of tetraethoxysilane, bis [3- (triethoxysilyl) propyl ] diselenide and absolute ethyl alcohol, wherein: the mass of the tetraethoxysilane is 4g, the mass of the bis [3- (triethoxysilyl) propyl ] diselenide is 1g, and the volume of the absolute ethyl alcohol is 2 mL; continuously stirring for 4 hours, collecting nano particles through centrifugation, and fully washing a solid crude product with absolute ethyl alcohol for three times; refluxing 1 wt% ammonium nitrate ethanol solution for 12 hours, centrifugally collecting, washing with ethanol for several times, repeatedly refluxing twice, and finally vacuum drying to obtain the bisselenium mesoporous silicon nanoparticles capable of responding to X-ray drug release.
Through transmission electron microscope and nitrogen adsorption and desorption curve detection, the diameter of the double-selenium mesoporous silicon (MON) nano particle capable of responding X-ray medicine release is 60nm, and the specific surface area is 432.7m2·g-1The pore diameter of the mesopores was 4.2nm, and the results are shown in FIGS. 1 and 2.
Example 2: degradation condition of double-selenium mesoporous silicon nano particles
100 μ g of the diselenide mesoporous silicon nanoparticles (i.e., the diselenide mesoporous silicon nanoparticles obtained in example 1) were irradiated with 1Gy of X-ray (irradiation time: 1 minute), and H was added thereto at a final concentration of 100 μ M2O2Incubating the aqueous solution at the constant temperature of 37 ℃ and the rotation speed of 200rpm for 72 hours, respectively carrying out X-ray irradiation for 0 hour (namely the diselenide mesoporous silicon nano particles obtained in the embodiment 1), 1Gy X-ray irradiation, and incubating for 72 hours, and then collecting samples for TEM detection;
through a transmission electron microscope, it is found that the diselenide mesoporous silicon (MON) nanoparticles can be rapidly degraded after being irradiated by low-dose X-rays, and the result is shown in fig. 3a, and then the diselenide mesoporous silicon (MON) nanoparticles continue to be slowly degraded under redox conditions, and the result is shown in fig. 3 b.
Example 3: release of mesoporous silica-loaded doxorubicin and DOX
(1) MON @ DOX drug loading and DOX release
50mg of Doxorubicin (DOX) was dissolved in 50mL of water to give a 1mg/mL stock solution. Suspending 50mg of mesoporous silicon carrier in prepared 50mL of DOX solution under ultrasound, oscillating the obtained mixture at 37 ℃ and 500rpm for 12 hours, centrifuging to obtain a solid, namely the double-selenium mesoporous silicon nanoparticles (MON @ DOX) loaded with the drug, and drying in vacuum at 30 ℃ for later use. The drug loading was analyzed by UV-Vis spectroscopy at 480nm, the supernatant was collected and the drug loading was calculated using the following formula:
in drug release assays, drug-loaded nano-delivery systems (MON @ DOX) were each placed at 0 μ M H2O2、100μM H2O2The PBS buffer solution and MON @ DOX were irradiated with 1Gy X-rays and then placed in a container of 100. mu. M H2O2In PBS buffer solution (0.01M pH7.4), oscillating at 37 deg.C and 100rpm, taking a small amount of buffer solution at intervals, analyzing the release amount of the drug at 480nm by ultraviolet-visible spectrum, simultaneously supplementing equal amount of buffer solution, pouring back to the release system, measuring the release rate at different time points within 96 hours, and drawing a release curve. The specific operation is as follows:
in the DOX release test, three portions of MON @ DOX, each 5mg, were dispensed separately, and two of the portions were each dispensed with MON @ DOX in 10mL portions containing 0. mu. M H2O2And 100 μ M H2O2In PBS buffer (pH 7.4); another set of MON @ DOX was irradiated with 1Gy of X-rays for 1 minute and then placed at 100. mu. M H2O2In PBS buffer (pH 7.4); the mixture was shaken at 37 ℃ and 100 rpm. The amount of DOX released in the supernatant was determined by uv-vis absorption spectroscopy at a wavelength of 480nm at 0, 1 hour, 2 hours, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, respectively.
The results are shown in fig. 4, where the drug is released rapidly after X-irradiation, and then slowly. Adding 100 mu M H2O2The group of PBS buffers showed only a relatively slow release. And 0 mu M H2O2The amount of the drug released in the PBS buffer of (1) was very small.
Example 4: anti-tumor effect of mesoporous silicon-loaded drug
The method of example 3 is followed to load the diselenide mesoporous silicon nanoparticles with adriamycin, 5-fluorouracil, paclitaxel, methotrexate and docetaxel drugs to form degradable mesoporous silicon nanoparticlesA delivery system. 4T1 cells (purchased from ATCC) in log phase were seeded at 5000 cells/well in 96-well plates at 37 ℃ with 5% CO2The cell culture box is used for culturing, and the drug is administered when the cell growth reaches 70-80% fusion. After 12 hours of administration, the single molecule drugs: doxorubicin, 5-fluorouracil, paclitaxel, methotrexate and docetaxel and the degradable mesoporous silicon nanoparticle drug delivery system are irradiated by 1Gy X-ray for 1 minute and then cultured for 12 hours; meanwhile, the monomolecular drug which is not radiated by X-ray and the degradable mesoporous silicon nano particle drug delivery system are used as contrast to continue culturing for 12 hours; in the experiment, the dosage of each monomolecular drug is ensured to be the same as the dosage of the corresponding drug in the degradable mesoporous silicon nano particle drug delivery system. The MTT method is used for evaluating the cell activity and verifying the inhibition effect of the monomolecular drug and the degradable mesoporous silicon nano drug delivery system on the growth of the tumor cytoplasm. The results are shown in Table 1.
Table 1: results of carrier mesoporous silicon nanomaterial loaded with different drugs on growth inhibition of 4T1 cells
Note that: the X-ray used was low dose (1Gy) radiation, with no significant cytotoxicity.
As can be seen from Table 1, compared with single-molecule drugs used together with X-ray radiation, the nano drug delivery system has stronger effect of inhibiting the growth of tumor cells, not only accelerates the release of the drugs, but also has the synergistic radiotherapy effect, and significantly increases the growth inhibition of the tumor cells.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A preparation method of mesoporous silicon nanoparticles capable of releasing drug in response to X-rays is characterized by comprising the following steps:
(1) preparation of bis [3- (triethoxysilyl) propyl ] diselenide
Dripping gamma-chloropropyltrimethoxysilane into the sodium diselenide solution, stirring at room temperature overnight, stopping reaction, extracting, drying, and purifying the crude product by chromatography to obtain a dark yellow liquid, namely bis [3- (triethoxysilyl) propyl ] diselenide;
(2) preparation of double-selenium mesoporous silicon nano particle capable of responding X-ray medicine release
Dissolving a cation template agent and triethanolamine, heating and stirring; and then adding a mixed solution of tetraethoxysilane, bis [3- (triethoxysilyl) propyl ] diselenide and ethanol to obtain a system 1, continuously stirring, centrifugally collecting the nanoparticles, washing a solid crude product, refluxing the ammonium nitrate ethanol solution, centrifugally collecting, and drying to obtain the diselenide mesoporous silicon nanoparticles capable of responding to X-ray drug release.
2. The production method according to claim 1,
the gamma-chloropropyltrimethoxysilane and the sodium diselenide in the step (1) are calculated according to the molar ratio of 2: 1;
the chromatography in the step (1) is silica gel column chromatography; the solvent for silica gel column chromatography is petroleum ether and dichloromethane is 10-1: 1;
the cationic template agent in the step (2) comprises at least one of hexadecyl trimethyl p-toluene ammonium sulfonate, hexadecyl trimethyl ammonium chloride and hexadecyl trimethyl ammonium bromide;
the dosage of the cationic template agent in the step (2) is 0.3-15 wt% of the system 1;
the dosage of the triethanolamine in the step (2) is 0.1-1.5 wt% of the system 1;
the using amount of the ethyl orthosilicate in the step (2) is 2-12 wt% of the system 1;
the usage amount of the bis [3- (triethoxysilyl) propyl ] diselenide in the step (2) is 1-5 wt% of the system 1;
the ethanol in the step (2) is absolute ethanol; the amount of the absolute ethyl alcohol is 2.5-10 wt% of the system 1.
3. A mesoporous silicon nanoparticle capable of releasing drug in response to X-rays is characterized by being prepared by the preparation method of any one of claims 1-2.
4. The use of the mesoporous silicon nanoparticles capable of releasing drug in response to X-ray as claimed in claim 3 in the preparation of an antitumor drug delivery system.
5. A degradable mesoporous silicon nanoparticle drug delivery system, which is characterized by comprising the mesoporous silicon nanoparticles capable of releasing drug in response to X-ray according to claim 3 and a drug; the mesoporous silicon nano particle capable of responding to X-ray release is used as a carrier for loading the drug.
6. The degradable mesoporous silicon nanoparticle drug delivery system according to claim 5, wherein the drug comprises a small-molecule antitumor drug and/or a derivative of a small-molecule antitumor drug.
7. The system according to claim 6, wherein the small-molecule antineoplastic drug and/or derivative of the small-molecule antineoplastic drug comprises at least one of adriamycin, paclitaxel, docetaxel, vincristine sulfate, 5-fluorouracil, methotrexate, mitoxantrone, adenosine cyclophosphamide, perlomycin sulfate, carmine, iminoquinone, aclarubicin hydrochloride, carmustine, temozolomide, lomustine, carmofur, tegafur, actinomycin D, mitomycin, amsacrine, amifostine, cisplatin, ararelin, aminoglutethimide, mechlorethamine hydrochloride, sorafenib, nilotinib, and dasatinib, and/or derivative of at least one of the above small-molecule antineoplastic drugs.
8. The preparation method of the degradable mesoporous silicon nanoparticle drug delivery system of any one of claims 5 to 7, comprising the following steps:
dissolving the medicine to prepare a medicine stock solution; dispersing the mesoporous silicon nanoparticles capable of releasing drug in response to X-rays of claim 3 into a drug stock solution under an ultrasonic condition to form a mixed solution; and carrying out shake culture on the mixed solution, and centrifuging to obtain a solid, namely the double-selenium mesoporous silicon nano particles loaded with the drug.
9. The use of the degradable mesoporous silicon nanoparticle drug delivery system of any one of claims 5 to 7 in the preparation of a medicament for cancer treatment.
10. The use of claim 9, wherein said treatment comprises at least one of chemotherapy, and a combination chemotherapy-radiotherapy treatment.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112957345A (en) * | 2021-02-07 | 2021-06-15 | 济南国科医工科技发展有限公司 | Light-operated drug release degradable temperature-sensitive mesoporous silicon nanoparticle system |
| CN113150028A (en) * | 2021-04-09 | 2021-07-23 | 浙江理工大学 | Preparation method of mesoporous organic silicon nanowire and mesoporous organic silicon nanowire |
| CN114224911A (en) * | 2021-11-26 | 2022-03-25 | 华南理工大学 | Nano material capable of efficiently removing cfDNA and ROS, and preparation method and application thereof |
| CN115089728A (en) * | 2022-06-16 | 2022-09-23 | 磐如生物科技(天津)有限公司 | Bladder cancer targeted nano-drug and preparation method thereof |
-
2020
- 2020-08-26 CN CN202010869738.7A patent/CN112057434A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| DAN SHAO等: "Bioinspired Diselenide-Bridged Mesoporous Silica Nanoparticles for Dual-Responsive Protein Delivery", 《ADV. MATER.》 * |
| 温雅静等: "辐射响应的化疗药物递送***用于肿瘤治疗的研究进展", 《药学进展》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112957345A (en) * | 2021-02-07 | 2021-06-15 | 济南国科医工科技发展有限公司 | Light-operated drug release degradable temperature-sensitive mesoporous silicon nanoparticle system |
| CN112957345B (en) * | 2021-02-07 | 2022-03-08 | 济南国科医工科技发展有限公司 | Light-operated drug release degradable temperature-sensitive mesoporous silicon nanoparticle system |
| CN113150028A (en) * | 2021-04-09 | 2021-07-23 | 浙江理工大学 | Preparation method of mesoporous organic silicon nanowire and mesoporous organic silicon nanowire |
| CN114224911A (en) * | 2021-11-26 | 2022-03-25 | 华南理工大学 | Nano material capable of efficiently removing cfDNA and ROS, and preparation method and application thereof |
| CN115089728A (en) * | 2022-06-16 | 2022-09-23 | 磐如生物科技(天津)有限公司 | Bladder cancer targeted nano-drug and preparation method thereof |
| CN115089728B (en) * | 2022-06-16 | 2024-01-26 | 磐如生物科技(天津)有限公司 | Bladder cancer targeted nano-drug and preparation method thereof |
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