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Chao Fang,1,* Daihan Xie,1,* Fanlei Kong,2,* Xin Yu,1 Jingting Yin,1 Yu Huo,3 Chunxia Su1 1Department of Comprehensive Oncology Center, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China; 2Department of Ultrasound in Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, People’s Republic of China; 3Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, 530222, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxia Su, Department of Comprehensive Oncology Center, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, School of Medicine, Tongji University, No. 507 Zheng-min Road, Shanghai, 200433, People’s Republic of China, Email susu_mail@126.com Yu Huo, Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, No. 13 Wu-He Avenue, Nanning, 530222, Guangxi Zhuang Autonomous Region, People’s Republic of China, Email huoyu_10@163.comPurpose: 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 Fe3⁺ 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