A Synergistic Nanoplatform for Chemodynamic and Sonodynamic Cancer Therapy

The development of non-invasive, synergistic therapeutic strategies remains a critical challenge in cancer treatment due to tumor heterogeneity and the limitations of monotherapies. Herein, we report a multifunctional zirconium-based metal–organic framework nanoplatform Zr-MOF-NH 2 @Pt@PEI, which was synthesized by the solvothermal method, followed by in situ growth of ultrasmall platinum (Pt) within the MOF matrix and subsequent surface modification with polyethyleneimine (PEI). A Schottky-type heterojunction was formed at the Pt-MOF interface, significantly enhancing charge separation, inhibiting electron-hole recombination, and maximizing reactive oxygen species generation under mild stimuli. The PEI coating conferred a strong positive surface charge, promoting cellular uptake via electrostatic interactions with cancer cell membranes while maintaining excellent hemocompatibility and cytocompatibility. Upon exposure to tumor microenvironmental H 2 O 2 and ultrasound stimulation, Zr-MOF-NH 2 @Pt@PEI effectively activated the synergistic anticancer effect of chemodynamic therapy and sonodynamic therapy. In conclusion, Zr-MOF-NH 2 @Pt@PEI is a promising candidate for non-invasive multimodal cancer therapy, providing a strategy for precise nanomedicine.