Dual functionalized amino poly(glycerol methacrylate) with guanidine and Schiff-base linked imidazole for enhanced gene transfection and minimized cytotoxicity

Abstract

Efficient transfection activity and minimal toxicity are of crucial importance to the development of gene delivery systems for practical applications. In this work, guanidine and Schiff-base linked imidazole dual functionalized poly(glycerol methacrylate) (IGEP) was firstly synthesized. Subsequent investigations revealed that this new biomedical material is capable of sufficiently binding to plasmid DNA (pDNA) and formulating optimal sized 100 nm nanoparticles with positive ζ potentials of 10–30 mV. Biological evaluations demonstrated the strategic use of guanidine resulting in enhanced cellular uptake and nuclear localization activities by virtue of its favorable affinity to the cellular membrane, and Schiff-base linked imidazole resulting in promoted endosomal escape and DNA cargo releasing behaviors, consequently leading to better transfection efficacy compared to PEI_25K in the targeted cells. Another noteworthy fact was guanidine and imidazole minimized cytotoxicity, hence, these advantageous features provided substantial information to construct a safe and efficient gene delivery carrier towards practical development.