Dynamic Iron Catalysis on Quantum Dots Enables Ultrasound-Controlled Multimodal Cancer Therapy

• • Atomically dispersed Fe on quantum dots (FAQD) enables efficient Fenton-like catalysis, decomposing H2O2 to O2 and generating ·OH, with Fe present as Fe(III) confirmed by XPS and EXAFS, showing no crystalline Fe2O3 phases. • • Optimal Ag doping at Ag:Zn ratio of 5:100 (Ag-5) maximizes singlet oxygen (1O2) yield under ultrasound, as measured by DPBF assay; higher Ag doping reduces yield due to increased bandgap and exciton recombination. • • In vitro, FAQD-1 (with MMP-cleavable PEG) shows negligible cytotoxicity without US, but under US and H2O2-enriched conditions, it induces substantial ROS production, leading to HeLa cell viability reduction and mitochondrial impairment. • • In vivo, FAQD-1 with US irradiation fully suppressed primary and abscopal tumors within two weeks, while triggering systemic immune responses: CD8+ and CD4+ T cell infiltration increased, Treg populations decreased, and IL-2 levels were over twice that of FAQD-1 alone.