Lipid-Engineered Small-Sized Metal-Organic Frameworks for Targeted Delivery of Anlotinib in Lung Cancer Treatment

Purpose: In this study, we report the design and evaluation of Anlo@MOF-Lipo (AML), a liposome coated, small sized MIL-101(Fe) metal-organic framework (MOF) for targeted delivery of the multi target tyrosine kinase inhibitor anlotinib in lung cancer treatment. Methods: In detail, the biomimetic liposome shell enhances nanoparticle biocompatibility, while the MIL-101(Fe) core enables pH responsive release of Fe 3 ⁺ under acidic tumor conditions, triggering Fenton-like reactions and generating cytotoxic reactive oxygen species. Anlotinib is encapsulated within the MOF pores for sustained, intratumoral release, suppressing the growth of tumors. Results: Characterization confirmed uniform liposome coating and sustained anlotinib release of AML. In vitro, AML demonstrated superior cellular uptake and cytotoxicity in lung cancer cells. In a murine subcutaneous tumor model, AML treatment achieved a greater tumor volume reduction than free anlotinib, with no observable systemic toxicity. Furthermore, in the orthotopic lung cancer model, AML achieved the most pronounced therapeutic efficacy among all treatment groups. Conclusion: This dual mode therapeutic strategy-combining targeted chemotherapy with oxidative stress induction-highlights the potential of AML as a promising nanomaterial for improving lung cancer treatment. Keywords: anlotinib, fenton-like reaction, lung cancer, metal-organic framework, targeted therapy