A drug loaded system based on mesoporous silicon and tetrahedron DNA

A technology of mesoporous silicon and tetrahedron, which is applied to preparations, antitumor drugs, and drug combinations for in vivo experiments, which can solve the problems of inability to completely remove and poor curative effect.

Inactive Publication Date: 2018-09-25
SUZHOU GENHOUSE PHARMA RES & DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The treatment options for glioma are mainly surgery, radiotherapy and chemotherapy, but surgical treatment cannot be completely resected due to its anatomical characteristics, and chemotherapy has few available drugs due to the existence of the blood-brain barrier, and the curative effect is not good

Method used

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  • A drug loaded system based on mesoporous silicon and tetrahedron DNA
  • A drug loaded system based on mesoporous silicon and tetrahedron DNA
  • A drug loaded system based on mesoporous silicon and tetrahedron DNA

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1. The targeting effect of the drug delivery system on tumor cells.

[0052] U87 MG cells and HBL-100 cells in the logarithmic growth phase were digested with 2.5% trypsin, counted, and the cell concentration was 1×10 4 100 μL was inoculated in a 96-well plate, and a blank group (unmodified silicon spheres loaded with paclitaxel), a control group (AS1411 modified silicon spheres loaded with paclitaxel) and an experimental group (tetrahedral DNA blocked loaded with paclitaxel silicon spheres) were set up. The next day, the blank group, control group and experimental group were added with different drug-loading systems. After 48 hours, the cells were lysed and the paclitaxel content in the cells was detected by HPLC. It can be clearly found that the content of paclitaxel in tumor cells is significantly higher than that in normal cells HBL-100, which proves that targeting tumor cells is effective.

Embodiment 2

[0053] Example 2. Sensitivity of the drug-carrying system to pH.

[0054] U87 MG cells in the logarithmic growth phase were digested with 2.5% trypsin, counted, and the cell concentration was 1×10 4 100 μL were inoculated in a 96-well plate, and the control group (a tetrahedral DNA structure constructed by random sequence modification loaded with paclitaxel silicon spheres and the sequence complementary to the random sequence) and the experimental group (AS1411 sequence modified loaded paclitaxel silicon spheres and i -motif sequence constructed tetrahedral DNA-enclosed loaded paclitaxel silica spheres). The next day, different drug-loading systems were added to the control group and the experimental group, and the pH value of the system was adjusted to 6.5. After 48 hours, the cells were lysed and the paclitaxel content in the cells was detected by HPLC. It can be clearly found that the content of paclitaxel in the cells of the experimental group is significantly higher than...

Embodiment 3

[0055] Example 3. The effect of the drug-carrying system on penetrating the blood-brain barrier.

[0056] Balb / C female mice (Shanghai Slack Animal Co., Ltd., clean grade).

[0057] The first group was the blank control group, and unmodified silicon spheres loaded with paclitaxel were injected into the tail vein;

[0058] The second group was the targeting glioma group, and the AS1411-modified silicon spheres loaded with paclitaxel were injected into the tail vein.

[0059] The third group was the blood-brain barrier group, and tetrahedral DNA-encapsulated silicon spheres loaded with paclitaxel were injected into the tail vein.

[0060] The mice were killed 48 hours after spraying the drug, and the brain tissue was taken out, and the content of paclitaxel was measured by HPLC. It was found that the content of paclitaxel in the brains of mice in the third group was significantly higher than that of the other two groups, indicating that the designed drug-loading system could p...

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Abstract

The invention designs a carrier based on mesoporous silicon, wherein the surface of the mesoporous silicon is modified with G-rich sequence DNA, paclitaxel is loaded, the tetrahedral structure is formed through DNA self-assembly, a C-rich sequence protruding from the tetrahedron is hybridized with the G-rich sequence on the mesoporous silicon surface, and holes are sealed. DNA modified with aminois reacted with polypeptide to form a DNA-polypeptide chimera, and the polypeptide has the function of mediating blood-brain barrier penetration. The structure of the C-rich sequence can be changed ina slightly acidic environment of tumor, the seal of the tetrahedron DNA is open, the G-rich sequence has the function of targeting glioma, and the paclitaxel has the treatment effect.

Description

technical field [0001] The present invention relates to penetration of the blood-brain barrier and the blood-brain barrier. Background technique [0002] Mesoporous silicon nanomaterials are a kind of inorganic nanomaterials with both regular pore structure and good biocompatibility. Research hotspots. In recent years, new methods for synthesizing mesoporous silicon nanomaterials using supramolecules as templates have emerged, and many new structures and compositions of mesoporous silicon nanomaterials have emerged. As a high-performance inorganic nanomaterial, mesoporous silicon has two surfaces, inside and outside, and has unique surface properties. Through a series of modifications, mesoporous silicon nanoparticles containing different functional groups can be obtained, which can effectively Improve its physical and chemical properties, so that it can better meet the applications in the fields of biomedicine and catalysis. Since MCM-41 type mesoporous silicon can be us...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/54A61K47/04A61K31/713A61K49/00A61P35/00A61K31/337
CPCA61K47/02A61K31/713A61K31/337A61K2300/00
Inventor 王奎锋周璐
Owner SUZHOU GENHOUSE PHARMA RES & DEV CO LTD
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