Novel intracellular response nanoparticle loaded with target gene siRNA and preparation method of novel intracellular response nanoparticle

Abstract

Disclosed is a novel intracellular response nanoparticle loaded with target gene siRNA. The novel intracellular response nanoparticle comprises a high-molecular polymer PDSA which wraps the target gene siRNA and is decomposed under the glutathione concentration in cytoplasm, and the nanoparticle at least simultaneously wraps two kinds of target gene siRNA, namely MGLL-siRNA and CB2-siRNA. The nanoparticle capable of releasing siRNA through decomposition under the cytoplasmic glutathione concentration is utilized, the defect of siRNA transmission in the prior art is overcome, intracellular glutathione can be quickly responded, and the siRNA transmission efficiency is improved. The nanoparticles simultaneously wrap MGLL-siRNA and CB2-siRNA, so that malignant phenotype genes of malignant tumors can be silenced, repolarization of tumor-related macrophages to anti-cancer phenotypes can be promoted, MGLL expression is knocked down to directly act on the malignant tumors for inhibition, and CB2 is knocked down to promote repolarization of the tumor-related macrophages to M1 type to synergistically resist tumors.

Description

technical field [0001] The invention relates to the technical field of biomedicine, and more specifically, relates to a novel intracellular responsive nanoparticle loaded with target gene siRNA and a preparation method thereof. Background technique [0002] RNA interference technology (RNA interference, RNAi) has developed rapidly in recent years and has been applied in the treatment of various diseases, including cancer treatment. Compared with the small-molecule targeted drugs in the existing tumor treatment technology, the target gene siRNA based on RNA interference technology will have better selectivity for the target, and can specifically bind to the target gene and down-regulate the expression of the target gene without affecting the target gene expression. The expression of other normal genes in cells has less toxic and side effects; when used in tumor therapy, siRNA can be used to specifically down-regulate the expression of genes that promote tumorigenesis and prog...

AI Technical Summary

Problems solved by technology

For cancer therapy based on RNAi technology, siRNA needs to overcome a series of physiological barriers in the delivery process, such as how to target tumor cells, penetrate tumor tissue and cell membrane, efficiently escape from endosomes, and effectively release siRNA in the cytoplasm; the process is complex, The technology is difficult, there are many links, and the cost is high, and it is not stable

Although siRNA can be delivered through traditional viral vectors to overcome various physiological barriers, it has defects such as difficult preparation, small siRNA capacity, poor targeting specificity, and strong immunogenicity, and because it causes irreversible changes to the host cell genome, it has potential Great biological risk, difficult to achieve practical application in clinical transformation

In addition, in the prior art, a single siRNA is often used to silence a tumor-promoting gene to achieve therapeutic purposes, but the occurrence and progression of tumors are often promoted by multiple genes, and silencing a single gene or only The effect of killing tumors may not be obvious

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