Preparation method of gene targeting delivery system for tumors with high CD44 expression

Abstract

Based on the present situation that chitosan (CS) nanoparticle gene targeting delivery technology is recently adopted, the invention provides a preparation method of a gene targeting delivery system for CD44 high-expression tumors. The preparation method of the invention comprises the following steps: (1) modifying oxidized hyaluronic acid HA to obtain hyaluronic acid HAD with aldehyde groups; themodification is chemical modification and there are two aldehyde groups; (2) preparing siRNA-coated chitosan nanoparticle CSNps-siRNA; (3) carrying out covalent cross-linking of HAD prepared in the step (1) onto the CSNps-siRNA prepared in the step (2) through a reaction between the aldehyde groups and amino groups; the mass ratio of HAD to CS is 1:50-1:500. Problems caused by loss of HA in the prior art are solved, and the basis for opening up a new way to gene therapy of CD44 high-expression tumors in clinic is provided in the invention.

Description

technical field [0001] The invention belongs to the field of medicine and relates to a gene carrier, in particular to a targeting gene carrier obtained by modifying chitosan nanoparticles with modified hyaluronic acid. Background technique [0002] Modern molecular biology studies have shown that the occurrence and development of tumors is a complex evolution process with multiple genes, multiple stages, and multiple steps. The root cause may be abnormal changes in gene structure and expression inside cells, involving the abnormality and accumulation of various proto-oncogenes, tumor suppressor genes, growth factors and their receptors, cell adhesion factors, and DNA repair genes. For example, Bcl2 is a proto-oncogene and one of the most important genes that inhibit tumor cell apoptosis. Studies have shown that the translocation and high expression of Bcl2 gene are closely related to the occurrence, development and poor prognosis of tumors. Reducing or eliminating the overe...

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Problems solved by technology

Yet, there is following problem in the method described in this application: (1) reaction temperature is high, is 40-70 ℃, easily causes the reduction of chitosan molecular weight; (2) the mass concentration range of hyaluronic acid in aqueous solution is little, only 1-5%, thereby limiting the amount of reaction; (3) after the completion of the reaction, repeated dialysis and washing treatments are required to obtain modified hyaluronic acid, and the operation is complicated; (4) the stirring reaction time is as long as 3-24h, resulting in The whole operation process takes a long time, which will easily lead to a decrease in the activity of the aldehyde group after the reaction

[0006] In addition, there is no report on the combination of oxidized hyaluronic acid and chitosan nanoparticles as a gene-targeted delivery system for tumors with high CD44 expression

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