Ultrasmall Ligand-Protected Ag7 Nanoclusters Enable Dual-Mode Reactive Oxygen Species Generation under Dark and Near-Infrared Irradiation

  • ACS Nano. 2026 Jun 9;20(22):16118-16134. doi: 10.1021/acsnano.6c01532.
Divinah Manoharan  1 ,  Kana Yamamoto  2 ,  Li-Chan Chang  3 ,  Chouma Kurihashi  4 ,  Issey Osaka  4 ,  Yin-Fen Liu  3 ,  Siou-Wei Liang  1 ,  Hideya Kawasaki  2 ,  Wen-Pin Su  3  5  6 ,  Chen-Sheng Yeh  1  5
Affiliations
  • 1. Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan.
  • 2. Department of Chemistry and Materials Engineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan.
  • 3. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
  • 4. Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Imizu, Toyama 939-0398, Japan.
  • 5. Center of Applied Nanomedicine, National Cheng Kung University, Tainan 701, Taiwan.
  • 6. Departments of Oncology and Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
PMID: 42208022 DOI: 10.1021/acsnano.6c01532
Abstract

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.

Keywords
ROS; chemodynamic therapy; photodynamic therapy; self-oxygenation; silver nanoclusters.
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