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An aptamer-modified oxygen-carrying drug-carrying multifunctional liposome complex

A liposome complex and multifunctional technology, applied in the field of medicine, can solve the problems of easily hindering cell uptake and reducing the efficiency of drug delivery, so as to reverse the drug resistance of tumor cells, improve the anti-tumor effect, and improve the tumor hypoxia microbe. The effect of the environment

Inactive Publication Date: 2020-04-10
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, PEGylation easily hinders cellular uptake and reduces drug delivery efficiency

Method used

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  • An aptamer-modified oxygen-carrying drug-carrying multifunctional liposome complex
  • An aptamer-modified oxygen-carrying drug-carrying multifunctional liposome complex
  • An aptamer-modified oxygen-carrying drug-carrying multifunctional liposome complex

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Dissolve 4 mg EDC and 8 mg NHS in 200 μL of secondary water, and then add 100 μL of a carboxy-modified aptamer targeting EGFR (10 μM, see the literature for its specific sequence Tan Y, Shi Y-s, Wu X-d, Liang H-y, Gao Y-b, Li S-j, et al. DNA aptamers that target human glioblastoma multiformecells overexpressing epidermal growth factor receptor variant III in vitro.Acta Pharmacologica Sinica. 2013;34(12):1491-8.), stirred at room temperature for 3h in the dark; Add 200 μL of 1% (v / v) chitosan solution to it, stir for 8 h, ultrafilter (MW=10000) three times, each time for 15 min, discard the filtrate, and dilute with PBS to make aptamer-modified chitosan ( Apt-Cs) suspension.

[0035] Weigh 20mg of lecithin, 5mg of cholesterol, 1.58mg of erlotinib and 200μL of PFOB in a pear-shaped flask, add dichloromethane to dissolve, and rotate under reduced pressure to form a lipid film; hydrate with the Apt-Cs suspension obtained above The lipid film was sonicated in an ice bath fo...

Embodiment 2

[0039] Weigh 20 mg lecithin, 5 mg cholesterol and 1.58 mg erlotinib in a pear-shaped flask, add dichloromethane to dissolve, reduce pressure and rotary steam to form a lipid film, and use the Apt-Cs suspension water prepared in Example 1 The lipid film was thawed and sonicated in an ice bath for 10 min to obtain a suspension of aptamer-modified drug-loaded liposome complex (ACLE) loaded only with erlotinib. The particle size of the synthesized ACLE was determined to be about 200 nm by a particle size analyzer.

Embodiment 3

[0041] Weigh 20 mg of lecithin, 5 mg of cholesterol and 200 μL of PFOB in a pear-shaped flask, add dichloromethane to dissolve, and rotate under reduced pressure to form a lipid film, and use the Apt-Cs suspension prepared in Example 1 to hydrate the lipid film , sonicated in an ice bath for 10 min to obtain a suspension of aptamer-modified oxygen-carrying liposome complexes (ACLP) loaded only with perfluorooctyl bromide. The particle size of the synthesized ACLP was determined to be about 200 nm by a particle size analyzer.

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Abstract

The invention discloses an aptamer modified oxygen-carrying and medicine-carrying multifunctional liposome compound. The compound contains a liposome, a chitosan derivative, an anti-cancer medicine and an oxygen-carrying body, wherein the liposome is prepared from lecithin and cholesterol, the chitosan derivative is fixed in the liposome and is fixed by a nucleic acid aptamer of a targeting epidermal growth factor receptor (EGFR), and the anti-cancer medicine and the oxygen-carrying body are entrapped in the liposome. The liposome compound can be prepared by virtue of a hydration film method, the method is simple and convenient, and obtained nano-particles have uniform particle sizes and good dispersity; and the liposome compound has good tumor targeting ability, presents a remarkable synergistic effect with medicine molecules and is capable of reversing drug resistance caused by hypoxia of tumor cells, and the tumor treatment efficiency is improved, and the liposome compound can be applied to the treatment of lung cancers.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an aptamer-modified oxygen-carrying drug-loading multifunctional liposome complex capable of reversing drug resistance of tumors. Background technique [0002] Cancer is one of the major diseases that seriously endanger human health, and its incidence has shown a significant upward trend in recent years. Lung cancer has one of the lowest survival rates of all cancers. Lung cancer is divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Non-small cell lung cancer is a common type of lung cancer, accounting for about 80-85% of all diagnosed lung cancer patients. Erlotinib is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and is a highly specific anti-tumor targeted therapy drug. Although erlotinib has achieved certain curative effect in the treatment of NSCLC, the resistance of tumor cells to it hinde...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K47/24A61K47/28A61K47/06A61K47/69A61K47/54A61K47/61A61K31/517A61K33/00A61P35/00
CPCA61K31/517A61K33/00A61K47/06A61K47/24A61K47/28A61K2300/00
Inventor 高瑜黎凤乔梅淏解晓东贾力
Owner FUZHOU UNIV
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