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 a NIR-II fluorescent probe that can be activated by 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 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 introduction of 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 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.