A polyethylenimine-mimetic biodegradable polycation gene vector and the effect of amine composition in transfection efficiency

The low toxicity and efficient gene delivery of polymeric vectors remain the major barrier to the clinical application of non-viral gene therapy. Here, we present a poly-d, l-succinimide (PSI)-based biodegradable cationic polymer which mimicked the golden standard, branched polyethylenimine (PEI, ∼25 kDa). To investigate the influence of 1°, 2°, 3° amine group ratio in the polymer, a series of PSI-based vectors (PSI-NN′x-NNy) grafted with different amine side chains of N,N-dimethyldipropylenetriamine (NN’) and bis(3-aminopropyl)amine (NN) were first characterized and contrasted by biophysical measurements. The in vitro and in vivo biological assay demonstrated that PSI-NN′0.85-NN1 exhibited better transfection ability and biocompatibility than PEI. The present results suggest that such PEI-mimic biodegradable PSI-NN′0.85-NN1 possesses a good potential application for clinical gene delivery.