Photothermally Controlled Gene Delivery by Reduced Graphene Oxide-Polyethylenimine Nanocomposite

Abstract

Externally stimuli-triggered spatially and temporally controlled gene delivery can play a pivotal role in achieving targeted gene delivery with maximized therapeutic effi cacy. In this study, a photothermally controlled gene delivery carrier is developed by conjugating low molecular-weight branched polyethylenimine (BPEI) and reduced graphene oxide (rGO) via a hydrophilic polyethylene glycol (PEG) spacer. This PEG–BPEI–rGO nanocomposite forms a stable nano-sized complex with plasmid DNA (pDNA), as confi rmed by physicochemical studies. For the in vitro gene transfection study, PEG–BPEI–rGO shows a higher gene transfection effi ciency without observable cytotoxicity compared to unmodifi ed controls in PC-3 and NIH/3T3 cells. Moreover, the PEG–BPEI–rGO nanocomposite demonstrates an enhanced gene transfection effi ciency upon NIR irradiation, which is attributed to accelerated endosomal escape of polyplexes augmented by locally induced heat. The endosomal escaping effect of the nanocomposite is investigated using Bafi lomycin A1, a proton sponge effect inhibitor. The developed photothermally controlled gene carrier has the potential for spatial and temporal site-specifi c gene delivery.