A novel versatile yolk-shell nanosystem based on NIR-elevated drug release and GSH depletion-enhanced Fenton-like reaction for synergistic cancer therapy

Abstract

In this study, a versatile doxorubicin (DOX)-loaded yolk-shell nano-particles (HMCMD) assembled with manganese dioxide (MnO₂) as the core and copper sulfide (HMCuS) as the mesoporous (∼ 6.4 nm) shell, was designed and synthesized. The resulting HMCMD possess excellent photothermal conversion efficiency. The DOX release from the yolk-shell nanoparticles could be promoted by laser irradiation, which increased the chemotherapy of DOX. Meanwhile, Mn²⁺ could be released from the HMCMD through a redox reaction between MnO₂ and abundant glutathione (GSH) in tumor cells. The released Mn²⁺ could promote the decomposition of the intracellular hydrogen peroxide (H₂O₂) by Fenton-like reaction to generate the highly toxic hydroxyl radicals (·OH), thus exhibiting the effective chemodynamic therapy (CDT). Additionally, the efficiency of Mn²⁺-mediated CDT could be effectively enhanced by NIR irradiation. Further modification of polyethylene glycol (PEG) would improve the water solubility of the HMCMD to promote the uptake by MCF-7 cells. Hence, the HMCMD with synergistic effects of chemotherapy and chemodynamic/photothermal therapy would provide an alternative strategy in antitumor research.

Keywords: Fenton-like reaction; MnO(2); NIR irradiation; Photothermal conversion; Synergistic therapy.