Photothermally Controlled Gene Delivery by Reduced Graphene Oxide-Polyethylenimine Nanocomposite

Externally stimuli-triggered spatially and temporally controlled gene delivery can play a pivotal role in achieving targeted gene delivery with maximized therapeutic efficacy. 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 confirmed by physicochemical studies. For the in vitro gene transfection study, PEG-BPEI-rGO shows a higher gene transfection efficiency without observable cytotoxicity compared to unmodified controls in PC-3 and NIH/3T3 cells. Moreover, the PEG-BPEI-rGO nanocomposite demonstrates an enhanced gene transfection efficiency 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 Bafilomycin A1, a proton sponge effect inhibitor. The developed photothermally controlled gene carrier has the potential for spatial and temporal site-specific gene delivery.