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Tumor self-targeting multilevel response type mesoporous silicon drug delivery system and preparation method thereof

A drug delivery system and tumor-targeting technology, which is applied in the field of tumor self-targeting multi-level responsive mesoporous silicon drug delivery system and its preparation, can solve the problem of discounting anti-tumor treatment effects, premature drug release, and harming normal tissues, etc. problems, to achieve the effects of reduced damage, improved endocytosis, stable and controllable drug release

Inactive Publication Date: 2020-06-09
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In practical applications, drug carriers that respond to a single stimuli often release the drug prematurely, resulting in greatly reduced anti-tumor therapeutic effects, and even harming normal tissues due to drug leakage.

Method used

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  • Tumor self-targeting multilevel response type mesoporous silicon drug delivery system and preparation method thereof
  • Tumor self-targeting multilevel response type mesoporous silicon drug delivery system and preparation method thereof
  • Tumor self-targeting multilevel response type mesoporous silicon drug delivery system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: Preparation and Characterization of Mesoporous Silicon Drug Delivery System with Temperature and pH Dual Response and Tumor Targeting

[0043] Such as Figure 1A As shown, the present invention provides a highly biocompatible tumor-targeting intelligent multi-response mesoporous silicon drug delivery system and its preparation method, including: synthesizing and preparing mesoporous silicon nanoparticles, loading anti-tumor drugs after silylation, Subsequently, N-isopropylacrylamide (NIPAm) and methacrylic acid (MAA) copolymers were covalently modified, and anti-HER2 single-chain antibodies were grafted to obtain nanoparticles with tumor targeting and dual responsiveness to temperature and pH.

[0044] Among them, by modifying the silane coupling agent MPS on the surface of the synthesized mesoporous silicon nanoparticles, anti-tumor drugs are loaded in the pores of the mesoporous silicon nanoparticles; the temperature and pH double response layer is modified ...

Embodiment 2

[0053] Example 2: Cytocompatibility and Hemocompatibility

[0054] The experimental steps are as follows:

[0055] Human breast cancer cells (SK-BR-3) with high expression of HER2 receptors were subcultured, spread on 96-well plates at 5,000 / well, and after 24 hours of incubation, MSN or MSN-pNIPAm / MAA-HER2 were added respectively to make The final particle concentration is 0, 5, 10, 50, 100, 200, 500 μg / mL, and continue to incubate for 24 hours;

[0056] Subsequently, remove the orifice plate and add tetramethylazolidine (MTT) to each well, and then put it in 37°C, 5% CO 2 Cultivate in the incubator for 4 hours;

[0057] Finally, take out the orifice plate and absorb the supernatant, add dimethyl sulfoxide (DMSO), shake for 10 minutes, measure the absorbance of each well with a microplate reader, record the relative cell viability when the concentration is 0 μg / mL as 100%.

[0058] Experimental results, such as Figure 3A As shown, at the same particle concentration, the ...

Embodiment 3

[0064] Example 3: Temperature and pH dual response drug release

[0065] Experimental steps:

[0066] Prepare pH 7.4 phosphate buffer (simulating human blood pH) and pH 5.0 phosphate buffer (simulating intracellular pH of human tumor tissue);

[0067] Disperse 2mg of DOX@MSN-pNIPAm / MAA-HER2 in phosphate buffer and react at 37°C and 25°C;

[0068] The supernatant was taken at a certain time interval, detected by a UV-visible spectrophotometer, and the cumulative release curve was drawn according to the ratio of the cumulative released drug amount to the total loaded drug amount at each time point.

[0069] Such as Figure 4 As shown, when high temperature (41°C) and acidic (pH 5.0) stimuli were used to jointly trigger drug release, the resulting drug release was faster and the release amount was higher than that of a single stimulus condition, indicating that the modified mesoporous Silicon nanoparticles have dual-response drug release behavior of temperature and pH, and hav...

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Abstract

The invention relates to a tumor self-targeting multilevel response type mesoporous silicon drug delivery system which includes mesoporous silicon nanoparticles. The mesoporous silicon nanoparticles are loaded with anticarcinoma drugs, and the surfaces of the mesoporous silicon nanoparticles are modified with polymer layers and low-toxicity tumor-targeting single-chain antibodies, so that the drugdelivery system has breast cancer cell targeting, temperature responsiveness and pH responsiveness. The invention further provides a corresponding preparation method. The tumor self-targeting multilevel response type mesoporous silicon drug delivery system has good biocompatibility, the specific targeting of HER2 highly expressing breast cancer cells and the controlled release of drug with temperature and pH dual response, and safe and controllable drug release can be achieved while tumor-specific identification is improved.

Description

technical field [0001] The invention relates to the fields of research and development of tumor targeting drugs and drug controlled release, in particular to a tumor self-targeting multi-level responsive mesoporous silicon drug delivery system and a preparation method thereof. Background technique [0002] In recent years, malignant tumors are still a major threat to modern humans, and chemotherapy is still a powerful means to fight against malignant tumors. In chemotherapy applications, nanoparticles have been widely developed as drug carriers to achieve more efficient drug delivery due to their excellent tissue penetration and drug loading capabilities. Among them, mesoporous silicon nanoparticles provide an ideal matrix for the design of functional drug carriers due to their high loading efficiency, good biocompatibility, and surface modification. [0003] However, pure nanoparticles are usually difficult to respond to changes in the physical, chemical, and physiological...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/04A61K31/704A61K9/50A61K47/58A61K47/68A61P35/00
CPCA61K9/501A61K31/704A61K47/58A61K47/6809A61P35/00
Inventor 陈超庄家丰王晓丽李辉王平马同昊汤文
Owner EAST CHINA UNIV OF SCI & TECH
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