Ultrasmall silver nanoclusters, Ag7 NCs protected by MBISA (MBISA = 2-mercapto-5-benzimidazolesulfonic acid sodium salt), are presented as a dual-mode nanoplatform enabling complementary reactive oxygen species (ROS) activity under dark and near-infrared (NIR) light conditions. In darkness, Ag7 NCs catalyze hydrogen peroxide decomposition through electronically differentiated Ag sites, concurrently generating hydroxyl radicals (•OH) and molecular oxygen (O2). XPS analysis demonstrates that the electronically differentiated Ag sites are preserved after H2O2 exposure, indicating chemical robustness rather than sacrificial oxidation. Under 730 nm NIR irradiation, photoexcited Ag7 NCs transfer energy to the in situ-generated O2, yielding singlet oxygen (1O2). The H2O2-driven O2 supply can functionally support subsequent 1O2 generation under NIR irradiation. This cooperative mechanism enables stimulus-dependent activation of complementary ROS pathways for synergistic chemo- and photodynamic therapy. Ag7 NCs exhibit excellent stability, renal clearance, and biosafety, achieving potent tumor regression and metastasis suppression in vivo. These findings position Ag7 NCs as a molecularly defined nanocluster platform with redox-active behavior and complementary ROS for precision cancer therapy.
Manoharan et al. (Thu,) studied this question.