Engineered exosome for high expression of cancer suppression miRNA and targeting lung cancer

Abstract

The invention provides an engineered exosome for high expression of cancer suppression miRNA and targeting lung cancer, and also provides a preparation method of the engineered exosome, and application of the engineered exosome to drug loading and targeting therapy in lung cancer disease treatment. The engineered exosome for high expression of cancer suppression miRNA and targeting lung cancer can stably carry lung targeting alpha6beta1 protein, and wraps miRNAs: miR-214 and miR-770 for inhibiting growth and metastasis of lung cancer, so that the engineered exosome can be targeted to the lung and inhibit the lung cancer, and experimental results show that the produced engineered exosome has the characteristic of targeting lung cancer and can be used for preparing the lung cancer targeted exosome. Compared with the prior art, the engineering stable cell line has the advantages that the quantity of the exosome entering the lung tissue is increased, meanwhile, the produced engineering exosome carries high-peak miR-214 and miR-770, the concentration of miR-214 and miR-770 in the lung tissue is increased, the growth and metastasis of the lung cancer can be effectively inhibited, and in addition, the engineering stable cell line is capable of preserving breeds, convenient in passage and capable of continuously producing the engineering exosome.

Description

technical field [0001] The invention relates to the technical field of engineered exosomes, in particular to an engineered exosome that highly expresses tumor suppressor miRNA and targets lung cancer. Background technique [0002] Exosomes are tiny vesicles with a lipid bilayer membrane structure, with a diameter of 30-150nm, which can be secreted by almost all cells and can mediate material exchange and information exchange between cells. Studies have shown that exosomes carry many In addition, exosomes have immunogenicity, a wide range of sources, and can carry various characteristics such as RNA, protein, DNA, and small molecules. Therefore, exosomes are loaded with drugs and targeted Treatment is a research hotspot for most diseases. [0003] At present, exosomes are often engineered to carry specific miRNAs by electroporation or specific transfection reagents, but these methods are often one-time, complicated and expensive, and cannot achieve stable and high-level miRN...

AI Technical Summary

Problems solved by technology

[0007] For the poor targeting of exosomes, after reinfusion into the body, the exosomes actually transported to specific tissues and organs are relatively small, and most of the exosomes enter other organs in the body through the blood circulation, which is equivalent to the injection of exosomes. The body is greatly diluted, and there is no accumulation of drugs in the organs that need treatment, which leads to the problem that the expected therapeutic effect cannot be achieved. The inventors found in the research that integrin α6β1 has lung targeting, is highly expressed and carries the exocytosis of α6β1 Physical fitness improves its accumulation in the lungs, and α6β1 itself can be spontaneously packaged on the exosome membrane, resisting lung cancer-related miRNAs, such as miR-302b, miR-214, miR-3180-3p, miR-770, miR-338 -3p, miR-let-7e, miR-613, etc. exist in exosomes, suggesting that overexpression of these specific miRNAs may increase miRNA kurtosis in exosomes

Images