Synergic therapy of melanoma using GNRs-MUA-PEI/siIDO2-FA through targeted gene silencing and plasmonic photothermia

Indoleamine dioxygenase 2 (IDO2) is a newly discovered enzyme that contributes to tumor immune escape. Our previous studies demonstrated that small interfering RNA (siRNA)-mediated IDO2 knock-down induces tumor cell apoptosis and inhibits tumor growth. Modified gold nanorods (GNRs) are excellent siRNA nano-carriers as well as photothermal therapy agents, with potential to augment siRNA efficacy and target specificity. In this study, we developed a novel nanostructure of GNRs-MUA-PEI/siIDO2-FA for targeted therapy of melanoma. Firstly, we demonstrated that these new nanostructures possess excellent biocompatibility, as well as efficiently and specifically deliver RNA to melanoma cells. Secondly, IDO2 knockdown significantly enhanced the photothermal therapeutic efficacy of GNRs as evidenced by inducing increased tumor cell apoptosis in vitro as well as inhibiting the growth of tumors in vivo under low laser power density. Finally, we firstly demonstrated that GNRs-MUA-PEI/siIDO2-FA exerts synergistic effects on photothermal therapy and gene silencing IDO2 in anti-tumor therapy of inhibiting tumor growth, which holds great promise for anti-cancer therapeutics as an alternative strategy for the treatment of melanoma.