Photothermally Responsive siRNA Delivery by PEGylated Poly(amido amine)s for Improved Tumor Therapy

Abstract

Polycations have a high siRNA binding efficiency, however, their cytotoxicity and poor transfection efficiency prevent their use in siRNA delivery. This study combined PEGylation for enhanced safety with a photothermally controlled endolysosomal escape to improve the cytoplasmic delivery of polycations.We first synthesized PEGylated cationic polymers (denoted as PEG-PHD), which were then used to prepare polyplexes with siRNA and ICG through electrostatic interactions. We found that the cytotoxicity of PEG-PHD and its polyplexes were significantly decreased compared with unPEGylated PHD. The prepared polyplexes successfully induced endolysosomal escape under laser irradiation, thereby showing better siRNA delivery efficiency in vitro and in vivo. Finally, polyplexes carrying siBcl-2 achieved significant inhibition of 4T1 tumor mediated by specific gene silencing after intravenous injection. In conclusion, this biocompatible photothermal controlled delivery platform is suitable for improving the efficiency of siRNA transfection. Overall, this study suggests that combing PEGylation and photoresponsive delivery is a promising strategy for designing siRNA delivery carriers.