Albumin-modified PAMAM self-assembly transgenic composition, preparation method and application thereof

Abstract

The invention discloses an albumin-modified PAMAM self-assembly transgenic composition, a preparation method and an application thereof. The invention provides a composition for transgenes. The composition of the invention is prepared by compounding a polyamide-amine dendritic polymer with an amino group on the terminal, albumin and nucleic acid. The composition of the present invention has the following advantages that: 1) the albumin is adopted to modify the PAMAM, such that the strong positive charge intensity of the PAMAM carrier can be reduced so as to reduce the cytotoxicity and the occurrence of the hemolytic phenomenon; 2) the albumin and the encytosis effect mediated by the cell-specific receptor are adopted, such that the cell targeting of the carrier is improved, the non-target cell uptake is reduced at a maximum, the effectiveness can be improved, and the toxic and side-effect can be reduced; 3) the albumin is adopted to modify the PAMAM, such that the biocompatibility of the PAMAM can be improved, therefore, the possibility of the PAMAM clearance by the reticuloendothelial system mediated by immune modification in vivo is reduced, and the in vivo circulation time of the PAMAM is increased.

Description

technical field [0001] The invention relates to an albumin-modified PAMAM self-assembled transgene composition, a preparation method and application thereof. Background technique [0002] With the in-depth understanding of the pathogenesis of major diseases and the development of molecular biology techniques, gene therapy has become a potential and powerful means of treating many diseases. At present, gene delivery vectors are mainly divided into two categories: viral vectors and non-viral vectors. Although the transfection efficiency of viral vectors is high, the further clinical application of viral vectors is limited due to many insurmountable shortcomings of viral vectors, such as toxicity, immunogenicity, inability to load large gene fragments, and biological safety. Non-viral vectors are safe and controllable, but have low transfection efficiency and lack of targeting. Therefore, how to achieve safe, efficient and targeted delivery of the target gene has become a hot...

AI Technical Summary

Problems solved by technology

[0005] Many studies have shown that the PAMAM nano-gene delivery system has a good application prospect in in vitro transfection, but there are still several problems to be solved in the in vivo application of PAMAM as a nano-gene delivery carrier: 1. The transfection efficiency is relatively low; 2. .In the in vivo environment, PAMAM can non-specifically bind a large number of negatively charged macromolecules and red blood cells, affecting the transfection efficiency and causing hemolysis; 3. Realize the targeting of PAMAM nano-gene delivery system

[0006] In order to solve the above problems, most of the current studies directly modify PAMAM molecules, such as modifying residues such as ornithine on the surface of PAMAM [Int J Pharm, 2010, 392: 294-303] to enhance the positive charge on the surface of PAMAM molecules to enhance Transfection efficiency, but this method also increases cytotoxicity while enhancing excess electropositivity; on the other hand, modify PEG [Nanotechnology, 2009, 20: 105103] on the surface of PAMAM to improve biocompatibility and reduce Non-specific binding to negatively charged macromolecules and red blood cells in plasma. In addition, specific proteins such as lactoferrin are modified at the end of PEG [Biomaterials, 2008, 29(2): 238-246] to achieve tissue targeting, but PEG The modification increases the steric hindrance of the combination of PAMAM molecules and DNA molecules, reducing the transfection efficiency

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