A facile and scalable method to synthesize PEGylated PDMAEMA for gene delivery

In recent years, cationic polymer vectors have been viewed as a promising method for delivering nucleic acids. With the advancement of synthetic polymer chemistry, we can control chemical structures and properties to enhance the efficacy of gene delivery. Herein, a facile, cost‐effective, and scalable method was developed to synthesize PEGylated PDMAEMA polymers (PEO‐PDMAEMA‐PEO), where PEGylation could enable prolonged polyplexes circulation time in the blood stream. Two polymers of different molecular weights were synthesized, and polymer/eGFP polyplexes were prepared and characterized. The correlation between polymers' molecular weight and physicochemical properties (size and zeta potential) of polyplexes was investigated. Lipofectamine 2000, a commercial non‐viral transfection reagent, was used as a standard control. PEO‐PDMAEMA‐PEO with higher molecular weight exhibited slightly better transfection efficiency than Lipofectamine 2000, and the cytotoxicity study proved that it could function as a safe gene vector. We believe that PEO‐PDMAEMA‐PEO could serve as a model to investigate more potential in the gene delivery area.