Virus-like structure gene vector, drug delivery system, and preparation method and application thereof

Abstract

The invention provides a virus-like structure gene vector, which comprises a cationic polymer, cyclodextrin-grafted poly (L-glutamic acid) and a hydrophilic polymer with an amantadine terminal group, when the virus-like structure gene vector is used for loading a gene drug, the negatively charged gene drug and the like and the positively charged cationic polymer form a cationic core through electrostatic interaction; poly (L-glutamic acid) grafted with cyclodextrin wraps the surface of the cation core to form a shielding layer, so that the core can be stabilized; the amantadine end group of the hydrophilic polymer is assembled to the surface of a particle through the host-guest interaction of adamantane and cyclodextrin, so that the core is better protected, the gene drug is prevented from being degraded, and meanwhile, the hydrophilic compound can endow the drug delivery system with other characteristic virus-like gene vectors with high transfection efficiency, simple structure and low cost. And the carrier can be widely used for carrying DNA, mRNA, siRNA, microRNA and the like. The invention also provides a drug delivery system, and a preparation method and application thereof.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a virus-like structural gene carrier, a drug delivery system, its preparation method and its application. Background technique [0002] Gene therapy is a promising treatment method, mainly through the repair or replacement of disease-causing genes by transferring genes into human cells to achieve the treatment of diseases. The key problem of gene therapy is to solve the problem of delivery of therapeutic nucleic acid, because if a single gene is directly injected into the body, it will be rapidly degraded and destroyed by substances and enzymes in body fluids, and it is difficult for the negatively charged macromolecular DNA itself to pass through the cell membrane and enter into the cells. Therefore, it is necessary to carry the target gene with the help of a gene carrier to complete the process of transporting to the target cell and entering the nucleofection. [0003] At...

AI Technical Summary

Problems solved by technology

For example, the prior art CN109152830A discloses a lipid bilayer-shielded core-shell structure mRNA delivery carrier, which can stabilize the inner core and promote macropinocytosis of the complex by antigen-presenting cells; however, lipid bilayer-coated After the compound is injected intravenously, it will accumulate in large quantities in the liver, making it impossible to achieve targeted delivery to other organs

Prior art CN 105906800A discloses a gene delivery system containing a pH-sensitive and breakable shielding material, which uses polyethylene glycol to shield the inner core complex; however, this shielding design has poor stability and is easy to enter the body after entering the body. fall off

Prior art CN 112641952A discloses a nucleocapsid gene delivery system containing a masking layer of polyethylene glycol and polyglutamic acid copolymer, which can obtain significant transfection efficiency in vivo; however, this masking layer is difficult to add target To the group, poor targeting of gene transfection

In summary, non-viral gene delivery vectors that can achieve stable masking and good in vivo targeting are still scarce

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