An H₂O₂ activated Ag₂S:In-Cu nanoprobe for in vitro synergistic tumor treatment

Ag₂S nanoparticles exhibit tremendous application potential in biomedical fields such as photothermal therapy (PTT) and photoacoustic imaging. However, they have certain drawbacks, including relatively weak near-infrared (NIR) absorption capacity and rather limited photothermal conversion efficiency. In this study, we designed an NIR-II fluorescent probe that can be activated by the tumor microenvironment (TME). Specifically, we first incorporated In³⁺ into Ag₂S nanoparticles, then allowed Cu²⁺ to complex with them, and finally encapsulated the resulting complexes with polyethylene glycol (PEG) (denoted as ACP). The incorporation of In³⁺ effectively mitigated the lattice defects of Ag₂S, significantly enhancing its NIR absorption capacity and thereby strengthening the therapeutic effect of PTT. Under 808 nm photoexcitation, the reaction of ACP nanoparticles with H₂O₂ exhibited a photothermal conversion efficiency of up to 67.8%. The introduced Cu²⁺ can react with the excessive H₂O₂ in tumor cells to generate highly oxidizing hydroxyl radicals (˙OH), enabling efficient chemodynamic therapy (CDT). Moreover, this process also depleted glutathione (GSH) within tumor cells, further disrupting the antioxidant defense system of tumor cells and greatly enhancing the therapeutic efficacy of CDT. This study offers a novel approach for utilizing responsive nanoparticles to enhance the dual synergistic in vitro effects of PTT/CDT.