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⁺ 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.