Preparation And Characterization Of Hypoxia Responsive Charge Reversal Gene Vector

Tumor cells are differentiated from normal cells and tissues due to their abnormal metabolism.Among them,due to the rapid metabolism of tumor cells,the slow angiogenesis,and the hypoxic characteristics of tumor sites,this is also an important reason for tumor resistance and recurrence.Gene therapy is a method of intervention that interferes at the molecular level,and is considered to be a very efficient treatment.Non-viral gene vectors have also been widely studied because of their good biological safety,low immunogenicity and easy modification.However,due to the high density of cations in non-viral vectors,their low transfection efficiency has been criticized.In the first part of this paper,a hypoxia-responsive charge-reversing polymer gene carrier was designed.If tumor cells in the hypoxic conditions,the concentration of nitroreductase will increase.The polymer is a cationic polymer containing 4-((4-nitrobenzyl)oxy)benzyl group,which can form nano-complexes by nucleic acid drugs through electrostatic action.After entering the cell,the polymer generates negatively charged polyacrylic acid under the action of nitroreductase,which quickly releases nucleic acid drugs through electrostatic action.The second part of the paper combines photothermal therapy with gene therapy,using indocyanine green(ICG)approved by FAD as a photothermal agent,and silencing the PKM2 gene by siRNA to block ATP energy supply,reducing the production of heat shock protein and increasing Light and heat treatment effect.At the same time,the cations are covered by liposomes to shield the surface charge,prolong the blood circulation time,and reduce the uptake of the reticuloendothelial system.The results of in vitro experiments show that the growth of 4T1 cells has a good inhibitory effect.