Nanocarrier Cross-Linking Density and pH Sensitivity Regulate Intracellular Gene Transfer

Treatment of diseases on the molecular level by genetic material is limited by effective delivery mechanisms. We focused on the synthesis of a pH-sensitive gene delivery vehicle based on dimethylaminoethyl methacrylate (DMAEMA) with tunable swelling, cross-linking density, and DNA release kinetics within the endosomal pH range. Our strategy, which utilized a single step for DNA encapsulation, enhanced gene transfection efficiency and reduced cytotoxicity relative to polyethyleneimine (PEI) and poly-L-lysine (PLL).