Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy

Journal of Nanobiotechnology

Wenhao Wang¹  Zhiyuan Zhang²  You Fu²  Kai Feng³  Yuanjing Xu⁴  Yifan Zhou⁵  Xin Wang⁵  Haohan Huang⁵  Yan Chen⁵  Hongfang Chen⁵  Haijun Tian⁵  Yuanqing Mao⁵  Jinwu Wang⁵ 

[1] College of Medicine, Southwest Jiaotong University, Chengdu, China;Department of Oral & Maxillofacial - Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China;Institute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, China;School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China;Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China;

关键词: Metal-organic framework (MOF);    Tumor hypoxia;    Photothermal therapy (PTT);    Osteosarcoma;   

DOI  :  10.1186/s12951-021-01013-0

来源: Springer

【 摘 要 】

BackgroundHypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier.ResultsThe results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1α pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1α expression while did not promote the expression of CD31 in vivo during the experiment.ConclusionsBy using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited.Graphic abstract

【 授权许可】

CC BY