An efficient photo-chemo combination therapeutic platform based on targeted reduction-responsive self-crosslinked polymer nanocapsules

Abstract

Photo-chemo combination therapy holds great promises for cancer treatment; thus developing efficient approaches for delivering photo-chemo combination reagents has long been pursued. Herein, an amphiphilic branched copolymer, four-arm poly(ethylene glycol)-poly(propylene sulfide)-cyclic(Arg-Gly-Asp-D-Phe-Lys) (PEG-PPS-cRGD), was synthesized to prepare targeted self-crosslinked polymer nanocapsules consisting of a disulfide bond and the α_vβ₃ integrin-targeting ligand cRGD. Furthermore, by coloading both indocyanine green (ICG) and doxorubicin (DOX) in PEG-PPS-cRGD nanocapsules, a high-performance photo-chemo combination therapeutic platform designated as DINCs was successfully developed. The dissolution rate investigations demonstrated that DINCs exhibited sensitive reduction-responsive drug release profiles during the incubation with glutathione (GSH), while the drug release rate could be further accelerated by NIR laser irradiation. The in vitro studies showed that DINCs had outstanding cellular uptake, photothermal effects and ROS generation under laser irradiation, which significantly enhanced cytotoxicity in the treatment of squamous cells (SCC-15). Moreover, the in vivo results showed that synergistic photo-chemo combination treatment by DINCs plus laser irradiation could completely eliminate the tumor of squamous cell carcinoma with favorable biological safety.