Stable gene transfection mediated by polysulfobetaine/PDMAEMA diblock copolymer in salted medium

Cationic polyplexes would aggregate immediately after intravenous injection due to the plasma proteins and high ionic strength. A cationic polyplexes with long-term and salt stability was very important for a systemic gene therapy. In this research, a polysulfobetaine-b-polycation diblock copolymer composed of cationic block of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and zwtterionic block of poly(propylsulfonate dimethylammonium ethylmethacrylate) (PSPE) was conveniently synthesized by atom transfer radical polymerization method to obtain a cationic polymers with long-term and salt stability. The results of agarose gel electrophoresis and transmission electron microscope indicated that copolymerization of PSPE did not compromise the DNA condensation ability of PDMAEMA, meanwhile exhibiting lower cytotoxicity. The effect of salt on the absorbance and particle size of PDMAEMA100/DNA and PDMAEMA100-PSPEy/DNA complexes was investigated, which showed that PSPE block could increase the resistance of polyplexes against salt-induced aggregation owing to the antielectrolyte effect. In comparison with PDMAEMA homopolymer, PDMAEMA100-PSPEy retained more stable gene transfection in a certain range of salt concentration. The expression of red fluorescence protein (RFP) was evaluated by small animal in vivo fluorescence imaging system and the results showed that the expression of RFP was much higher in the mice injected with PDMAEMA100-PSPE20/pDNA-RFP than with PDMAEMA/pDNA-RFP. Both in vitro and in vivo results suggested that PDMAEMA-PSPE diblock copolymer may be potentially used as a vector for systemic gene therapy.