Multifunctional polypeptide/liposome/hyaluronic acid-assembled virus-like nucleic acid vector

Abstract

The invention discloses a multifunctional polypeptide / liposome / hyaluronic acid assembled viroid nucleic acid carrier. The specific building method of the carrier comprises the steps that multifunctional polypeptide and cationic liposome are mixed, and then nucleic acid is added in the mixture for self-assembling to form nanoparticles with positive charge on the surface; polyanions are wrapped on the surfaces of the nanoparticles through the electrostatic interaction, and therefore the viroid nucleic acid carrier is assembled. The carrier has the advantages that by means of the human body safe biological materials, the novel non-viral carrier is built, wherein the novel non-viral carrier can tightly wrap nucleic acid and in-vivo long-term cycle and efficient targeting cancer cells, smoothly break through a cytomembrane and an endosome membrane to enter cytoplasm through the lipidosome membrane melting effect, release nucleic acid in the subacid cytoplasm through disassembling and self-degradation or enter a cell nucleus in a nanoparticle mode by changing a polypeptide sequence.

Description

technical field [0001] The present invention relates to a drug delivery technology in the field of drug technology, in particular to a construction and preparation technology of a non-viral vector system that can be used for in vivo system delivery of nucleic acids (DNA, siRNA, microRNA, shRNA, etc.), and specifically relates to a Multifunctional polypeptide / liposome / hyaluronic acid-assembled virus-like nucleic acid vector. Background technique [0002] In gene therapy, the key bottleneck for nucleic acid drugs from conception to clinical application is the development of its in vivo delivery system. Among them, non-viral vectors are mainly polycationic and cationic liposomes. Compared with viral vectors, they have low cost, high gene loading density and molecular weight, and simple preparation, except that the carrier itself has no biological safety hazards. It has the advantages of being convenient for chemical modification, but also has the disadvantages of high chemical...

AI Technical Summary

Problems solved by technology

The disadvantage is that in addition to the high toxicity of polycations, this type of carrier still achieves long-term circulation in the body and targets specific tissues by chemically grafting polyethylene glycol (PEG) and targeting groups on the peripheral cationic liposomes. Receptors on the cell surface, a large number of experimental results show that the effect of this type of carrier in vivo is not ideal

Among them, the multifunctional receptor-targeted nanoparticles prepared by Professor Hart, S.L. use polypeptides and liposomes to realize the biocompatibility of the carrier in vivo and greatly reduce the toxicity, and use polypeptides to encapsulate nucleic acids while targeting the cell surface receptors, but it has no new advantages in shielding charges, and still needs to participate through PEGylated liposomes, because the amount of PEG directly determines whether the carrier can circulate in the body for a long time, which complicates the problem

At present, there is no new carrier that can break through the common shortcomings of the ternary complex

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