EGFR-oriented monoclonal antibody modified PAMAM self-assembled transgenic composition and applications thereof

Abstract

The invention discloses an EGFR-oriented monoclonal antibody modified PAMAM self-assembled transgenic composition and applications thereof. The invention provides a composition for nucleic acid transgenosis, which is prepared by compounding a polyamidoamine-dendritic polymer of which the tail end is provided with amines, an EGFR-oriented monoclonal antibody, and a nucleic acid. The composition disclosed by the invention has the following advantages that 1) by taking an epidermal growth factor receptor (EGFR) as a therapeutic target, and using a monoclonal antibody and tumor cell EGFR induced endocytosis, the targeting of a PAMAM carrier to cells is increased; 2) through the modification of PAMAM by the monoclonal antibody (mAb), the ultra-strong positive charge intensity of the PAMAM carrier can be reduced, thereby facilitating the reduction of occurrence of cytotoxicity and hemolysis phenomena; and 3) an mAb / PAMAM G5 / DNA composition is prepared by using a self-assembling method, and compared with chemical synthesis, the molecular self-assembling method can carry out modification on a system more conveniently and flexibly, and keep the bioactivity of ligands.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a PAMAM self-assembled transgene composition modified by a monoclonal antibody against EGFR and its application. Background technique [0002] The emerging gene therapy method is to transfer exogenous gene fragments such as plasmid DNA, oligonucleotide, and small interfering RNA into the cell, regulate gene expression to correct the structural or functional disorder of the human gene, and prevent the progression of the disease. progress, kill diseased cells, so as to achieve the purpose of treatment. Because gene therapy can overcome the bottleneck of traditional treatment methods, gene therapy technology has been highly valued by various scientists and governments since its inception, and its development has been particularly rapid. , major malignant infectious diseases, genetic diseases) frontiers and hotspots. [0003] Vector technology has always been one of the core areas of g...

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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 transfection efficiency and causing hemolysis; 3) How to realize the targeting of PAMAM nano-gene delivery system

[0006] In order to solve the above problems, current studies mostly 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 the surface of PAMAM with PEG [Nanotechnology,2009,20:105-103] to improve biocompatibility , to reduce non-specific binding to negatively charged macromolecules and erythrocytes in plasma, and to modify specific proteins such as lactoferrin [Biomaterials,2008,29(2):238-246] at the end of PEG to achieve tissue targeting, but The modification of PEG increases the steric hindrance of the combination of PAMAM molecules and DNA molecules, reducing the transfection efficiency

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