Degradable hybrid CuS nanoparticles for imaging-guided synergistic cancer therapy via low-power NIR-II light excitation

Abstract

Near-infrared (NIR)-II light-excitable photonic agents capable of generating tumor hyperthermia and cytotoxic free radicals are promising for synergistic phototherapy of tumors. However, the lack of NIR-II excitable agents makes it challenging to achieve combinational tumor phototherapy. Here, the authors have reported on a tumor-targeting and degradable hybrid copper sulfide (CuS) nanoparticle (AIBA@CuS-FA) via loading a hydrophilic Azo initiator (AIBA) into an amphiphilic lipid-encapsulating CuS nanoparticle. AIBA@CuS-FA shows high photothermal conversion efficiency (PCE ≈ 47.5%) at 1064 nm, enabling heat production to trigger tumor hyperthermia and thermal decomposition of AIBA into cytotoxic free alkyl radicals upon irradiation with a 1064-nm laser under low-power density (0.5 W/cm2). Moreover, alkyl radicals can drive degradation of AIBA@CuS-FA and embedded CuS nanodisks, releasing Cu2+ ions that can catalyze a Fenton-like reaction for hydroxyl radical (•OH) production to promote tumor therapy. Findings demonstrate promise for combinational photothermal therapy (PTT), oxygen-independent alkyl radical therapy, and chemodynamic therapy (CDT) of tumors.