Preparation method of targeted extracellular vesicles for treating drug-resistant tumors

Abstract

The invention discloses a preparation method of targeted extracellular vesicles for treating drug-resistant tumors. The preparation method comprises the following steps: 1, preparing DOX-loaded EVs; 2, preparing a hyaluronic acid derivative with a targeting CD44; and 3, modifying the surface of the DOX-loaded EVs with a hyaluronic acid derivative with targeting CD44. The extracellular vesicles arederived from non-tumor cells and can reduce the acetylation level of histone H3 in a promoter region of a drug-resistant gene ABCB1 by inhibiting protein expression of histone acetylation transferase, so that the expression of drug-resistant protein P-gp is reduced. The invention also relates to targeted modification of extracellular vesicles by using hyaluronic acid connected with octadecyl. Theobtained targeting modified extracellular vesicles are simple in preparation process, good in biocompatibility and good in tumor cell targeting performance as a drug carrier, the permeability in tumor vessels is improved, the tumor drug resistance reversing effect is remarkable, and the targeting modified extracellular vesicles are an excellent drug carrier for treating drug-resistant tumors.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a method for preparing targeted extracellular vesicles for treating drug-resistant tumors. Background technique [0002] Tumor is currently a common disease that seriously threatens human health. Chemotherapy is an important clinical method for treating tumors. However, the chemotherapy resistance of tumor cells often leads to the failure of chemotherapy. The formation mechanism of drug resistance is complex, in which the overexpression of P-glycoprotein (P-gp) encoded by the multidrug resistance gene (ABCB1) is the main reason for cell drug resistance, and energy-dependent P-gp can pump drugs out of the cell. Reduce intracellular drug accumulation, leading to drug resistance of tumor cells. [0003] Extracellular vesicles are membranous vesicles with a diameter of 50-1000 nm released by cells to the extracellular environment, containing specific bioactive molecules from the...

AI Technical Summary

Problems solved by technology

[0008] The purpose of the present invention is to provide a method for preparing targeted extracellular vesicles for treating drug-resistant tumors, so as to solve the problem that there is no safe and effective non-tumor-derived EVs used to reverse tumor drug resistance in the prior art , and the method of modifying the cell membrane first, and then using mechanical force to break the cells to prepare EVs may destroy the modified targeting molecules or cause the targeting molecules to fall off

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