Fe-Doped Carbon Dots Control the Biodegradation Behaviors of Zr-Based Metal-Organic Framework for Tumor-Specific Chemotherapy and Ferroptosis Enhanced Sono-Chemodynamic Therapy.

Zr-based metal-organic frameworks (Zr-MOF) with proper bandgap structure and excellent biocompatibility has recently been identified as a desired drug carrier and sonosensitizers for the application of drug delivery and sonodynamic therapy (SDT). However, the fast degradable behaviors of Zr-MOF not only in acidic tumor microenvironment (TME) but also in normal physiological conditions can lead to strong off-target toxicity. To realize tumor-specific drug release, herein, it reports for the first time the regulation of degradation behaviors of Zr-MOF using Fe-doped carbon dots (Fe-CDs) with excellent chemodynamic/sonodynamic activities as a protection layer. The obtained DOX/Zr-MOF/Fe-CDs possesses TME-responsive degradation feature, which avoids the degradation of Zr-MOF under normal physiological conditions. In addition, the deposition of Fe-CDs not only improves the sonodynamic activity of Zr-MOF owing to the formation of Z-scheme heterojunctions, but also endows the novel nanoplatform with excellent chemodynamic activity. After completing SDT process, DOX/Zr-MOF/Fe-CDs can respond to acidic TME to specifically degrade and release Fe-CDs and DOX, which thereby triggered tumor-specific ferroptosis and chemotherapy. Significantly, the single treatment of DOX/Zr-MOF/Fe-CDs successfully eradicates tumors through tumor-specific chemotherapy and ferroptosis amplified SDT/CDT. This work presents an innovative strategy for the regulation of degradation behaviors of nanocarriers to realize tumor-specific drug release and enhanced combination tumor therapy.