摘要
A ZIF-based nanocomplex co-loaded with CaO₂ and curcumin to enhance ultrasound-induced cavitation. • Porous ZIF initiates cavitation; CaO₂ amplifies it to enhance tumor disruption. • Amplified cavitation releases antigens; curcumin inhibits CAFs; Ca(OH)₂ neutralizes acidosis to reprogram immunity. Immunotherapy for colorectal cancer remains challenging due to insufficient immunogenic cell death (ICD), poor immune cell infiltration, and an immunosuppressive tumor microenvironment. Ultrasound-induced cavitation generates localized high-energy microjets and elevated temperatures, offering a promising approach for disrupting tumor tissues and inducing burst antigen release. However, conventional cavitation enhancers, such as metal-organic frameworks (MOFs), suffer from limited bubble nucleation efficiency, which reduces their therapeutic impact. To address this limitation, we developed ZIF nanocomplexes co-loaded with calcium peroxide (CaO 2 ) and curcumin. Upon ultrasound activation, the porous ZIF framework rapidly initiates cavitation while releasing its cargo. CaO 2 reacts with interstitial fluid to produce oxygen and calcium hydroxide. The generated oxygen bubbles amplify cavitation intensity, thereby enhancing tumor tissue disruption and curcumin-mediated inhibition of cancer-associated fibroblasts (CAFs) barriers. Concurrently, calcium hydroxide neutralizes tumor acidosis, reprograms the tumor microenvironment and promotes cytotoxic T-cell infiltration. Unlike conventional acoustic cavitation, this approach utilizes self-amplified bubble dynamics to induce robust antigen release and ICD. The synergistic integration of cavitation-enhanced physical disruption, CAFs inhibition, and immune modulation achieved significant tumor suppression in colorectal cancer models with minimal systemic toxicity, establishing a novel paradigm for ultrasound-driven cancer immunotherapy. Download: Download high-res image (160KB) Download: Download full-size image
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