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

A technology for targeting cells and tumor cells, applied in anti-tumor drugs, pharmaceutical formulations, medical preparations with non-active ingredients, etc. The effect of reducing efflux and reducing toxic side effects

Inactive Publication Date: 2020-08-18
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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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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  • Preparation method of targeted extracellular vesicles for treating drug-resistant tumors
  • Preparation method of targeted extracellular vesicles for treating drug-resistant tumors
  • Preparation method of targeted extracellular vesicles for treating drug-resistant tumors

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[0052] The technical solution solved by the present invention relates to a preparation method and application of a drug carrier capable of targeting and reversing tumor drug resistance EVs. The drug carrier is composed of three parts. Among them, the chemotherapeutic drug used in this study is a broad-spectrum anti-tumor drug doxorubicin hydrochloride, the main body of the carrier is EVs extracted from non-tumor cells, and the tumor targeting group is octadecylamine and A hyaluronic acid derivative formed by linking hyaluronic acid. The preparation method comprises the following steps:

[0053] Step 1. Prepare DOX-loaded EVs. EVs are derived from the culture supernatant of the non-tumor cell line HEK293T cells, and are obtained by combining ultraviolet irradiation and co-stimulation with drug DOX;

[0054] Step 2, preparing hyaluronic acid derivatives targeting CD44;

[0055] Step 3, modifying the hyaluronic acid derivatives targeting CD44 on the surface of DOX-loaded EVs. ...

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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...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/46A61K47/36A61K31/704A61P35/00
CPCA61K9/1273A61K31/704A61K47/36A61K47/46A61P35/00
Inventor 王琳王征刘佳叶之兰常炳程赵镭向梦茜李琪琳邓炎
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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