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Method for preparing meso-porous silicon nano medicine carrier with cell specificity target, reduction responsiveness and triple anticancer treatment effects

A nano-drug carrier and mesoporous silicon technology, applied in the field of medical materials, can solve problems such as insufficient solution and unsatisfactory tumor inhibition efficiency, and achieve the effect of no special equipment requirements, strong versatility, and broad clinical application value.

Inactive Publication Date: 2014-09-03
CHONGQING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, relying solely on the "passive" targeting mechanism provided by the structural characteristics of tumor tissue is not enough to solve the unsatisfactory tumor suppression efficiency and systemic side effects in clinical chemotherapy

Method used

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  • Method for preparing meso-porous silicon nano medicine carrier with cell specificity target, reduction responsiveness and triple anticancer treatment effects
  • Method for preparing meso-porous silicon nano medicine carrier with cell specificity target, reduction responsiveness and triple anticancer treatment effects
  • Method for preparing meso-porous silicon nano medicine carrier with cell specificity target, reduction responsiveness and triple anticancer treatment effects

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: Preparation of mesoporous silicon / cytochrome c-aptamer DNA multifunctional nanocomposite particles with both reduction responsiveness and targeting

[0027] 1) Synthesis of mesoporous silicon nanoparticles: 1 g of cetyltrimethylammonium bromide and 0.28 g of sodium hydroxide were fully dissolved in 480 mL of distilled water, vigorously stirred and heated to 80° C. to obtain an 80° C. solution. Add 5 g of tetraethyl orthosilicate dropwise to the above solution at 80°C with a uniform injector to form a mixed solution, and stir vigorously for 2 hours until the mixed solution turns into a white suspension.

[0028] 2) Synthesis of carboxylated mesoporous silicon nanoparticles: 1.0 mL of 3-(triethoxysilyl)propyl succinic acid was slowly added dropwise to the white suspension in step 1), and after stirring in a water bath for 4 h, The crude product of carboxylated mesoporous silicon nanoparticles (CTABMSNs-TPS) was obtained by centrifugation. Then, evenly disperse...

experiment example 1

[0033] Experimental example 1: Reduction-responsive behavior of mesoporous silicon / cytochrome c-aptamer DNA multifunctional nanocomposite system

[0034] In this study, FITC was used as a model drug, and threothiobiitol (DTT) was used as a reducing stimulus signal to investigate the release behavior characteristics of the mesoporous silicon / cytochrome C-aptamer DNA nanocomposite system.

[0035] Two groups of subjects need to be produced. Among them, the first group needs to prepare the aptamer DNA functionalized reduction-responsive cell-targeting mesoporous silicon / cytochrome C composite system according to the steps in Example 1. Only in step 4), 10 mg of FITC was dissolved in 20 mL of PBS (pH=6.0) buffer solution, and 0.05 M DTT was also added. The second group also needs to prepare the aptamer DNA-functionalized reduction-responsive cell-targeting mesoporous silicon / cytochrome C composite system according to the steps in Example 1. Only in step 4), only 10 mg of FITC wa...

experiment example 2

[0037] Experimental Example 2: Efficiency of Mesoporous Silicon / Cytochrome C-Aptamer DNA Multifunctional Nanocomposite Particles in Targeting Liver Cancer Cells

[0038] Select the FITC-labeled mesoporous silicon / cytochrome c-aptamer DNA multifunctional nanocomposite particles prepared in Example 1, and monitor the endocytosis of liver cancer cells (HepG2) using transmission electron microscopy, laser confocal scanning microscopy, and flow cytometry Intracellular distribution of nanocomposite particles. Such as image 3 Shown: flow cytometry quantitative analysis shows ( image 3C), liver cancer cells were co-cultured with MSNsFITC and MSNs-CytC-AptFITC respectively. After 2 hours, among the cells incubated with MSNsFITC, the cells with fluorescent signals accounted for about 21.3%, while the cells with fluorescent signals in the MSNs-CytC-AptFITC group accounted for 48.7%; after 4 hours, among the cells in the MSNsFITC group, the cells with fluorescent signals accounted for...

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Abstract

The invention discloses a method for preparing a meso-porous silicon nano medicine carrier with cell specificity target, reduction responsiveness and triple anticancer treatment effects. The method comprises the following steps: firstly, synthesizing meso-porous silicon nano particles by using a gel dissolution method, subsequently, introducing a disulfide bond onto the surface of a meso-porous silicon nano reservoir by using a chemical modification method, innovatively fixing cytochrome C with an apoptosis-inducing function onto the surface of the meso-porous silicon nano reservoir, blocking meso-porous channels with medicines, finally modifying DNA (Deoxyribose Nucleic Acid) aptamer single chain molecules (AS1411, with a cancer cell apoptosis-inducing function) onto the surface of a meso-porous silicon / cytochrome C nano composite system, and taking the system as specificity ligand of a receptor (nucleolin protein) which is overexpressed on the surface of liver cancer cytomembrane, thereby establishing a multifunctional composite type nano medicine carrier system for achieving triple anticancer treatment under combined action of medicines, blocking substances and target molecules inside meso-pores.

Description

technical field [0001] The invention belongs to the field of medical materials, and relates to a method for constructing a multifunctional medical nanocarrier used for antitumor treatment. Background technique [0002] After more than half a century of exploration and progress, the potential application value of intelligent drug controlled release system in the medical field has fully emerged and has received increasing attention. Controlled-release drug delivery has gradually become an important branch of biomedical research, which spans many interdisciplinary disciplines such as chemical engineering, materials science engineering, biology, pharmacy, and clinical medicine. With the introduction of the EPR effect, anticancer drug carriers of micro-nano size have attracted more and more attention. However, relying solely on the "passive" targeting mechanism provided by the structural characteristics of tumor tissue is not enough to solve the unsatisfactory tumor suppression ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/04A61K47/26A61K47/42A61K9/14A61P35/00
Inventor 蔡开勇张蓓璐罗忠刘军杰
Owner CHONGQING UNIV
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