Green-Reduced Biodegradable Core–Shell Smart-Responsive MOFs for Photothermal-Enhanced Chemo–Chemodynamic in Tumor Catalysis Therapy

Metal-organic frameworks (MOFs) have been widely developed for the treatment of malignant tumors due to their high porosity, ease of functionalization, and smart-responsive degradation. Herein, a core-shell nanocomposite PAZDH (HA@DOX-PDA@Bio-Ag/ZIF-8) based on polydopamine (PDA)-coated green-reduced silver nanoparticles (Bio-Ag NPs) loaded on zeolite imidazolium framework-8 (ZIF-8) is designed, which can trigger near-infrared light (NIR)-enhanced chemodynamic reaction and chemotherapy for effective tumor treatment. Due to the targeting of the shell to the CD44 receptor, which is overexpressed in tumor cells, PAZDH NPs can actively aggregate at the tumor site. Subsequently, based on the pH-sensitive degradation of the core, this nanocomposite can release Bio-Ag NPs and doxorubicin (DOX) in a smart-responsive manner. Moreover, Bio-Ag NPs prepared by the green-reduced method using plant extract have a particle size of 40 nm, which can easily enter the tumor cells by endocytosis and induce apoptosis by catalyzing the production of cytotoxic ·OH from H₂O₂ enriched in the TME. Importantly, the high temperature generated by PTT can promote the release of DOX and accelerate the generation rate of ·OH, enabling photothermal-enhanced chemo-chemodynamic therapy. The PAZDH NPs can efficiently induce tumor ablation and inhibit solid tumors by up to 91.72%. In conclusion, this study provides a promising strategy for the development of smart-responsive MOFs in the field of tumor treatment.