Engineered Cancer Cell Membrane-Functionalized Metal-Organic Frameworks for Irinotecan/Curcumin Codelivery in Colorectal Cancer: Enhanced Efficacy and Mitigated Toxicity

Purpose: Irinotecan (CPT-11), a semisynthetic camptothecin derivative and topoisomerase I inhibitor, is globally used for treating cancers such as colorectal cancer. However, its clinical application is limited by severe adverse effects, including diarrhea and myelosuppression. Biomimetic nano-drug delivery is widely used and can improve chemotherapeutic activity and decrease side effects. Methods: In this study, we developed a cancer cell membrane-functionalized metal-organic frameworks for irinotecan/curcumin (named MZCC) for colorectal cancer treatment. In this study, by combining irinotecan, curcumin, MOFs and functionalized cancer cell membrane, a pH-sensitive drug delivery system of MZCC was developed for colorectal cancer treatment with enhanced chemotherapeutic efficacy while reducing side effects. The characteristics and stability of MZCC were carefully examined, and its anti-cancer efficiency was studied in vitro and in vivo. In vivo experiments in a murine colorectal cancer mouse model given intratumorally MZCC injection every 4 days were used to assess antitumor efficacy and systemic toxicity. Results: The MZCC system improved treatment antitumor efficacy by 2.3-fold compared with free CPT-11 through synergistic chemotherapy. MZCC-treated groups exhibited a significant reduction in inflammatory cytokine levels within colon tissues; inflammation levels decreased by 55% compared with free CPT-11, and colon length was restored to 79% of normal. Conclusion: Our strategy effectively alleviates CPT-11-induced intestinal toxicity and mitigates adverse reactions. This approach may provide a novel method for enhancing chemotherapeutic efficacy while reducing gastrointestinal toxicity.