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

• Main Authors: Hongfang Chen, You Fu, Kai Feng, Yifan Zhou, Xin Wang, Haohan Huang, Yan Chen, Wenhao Wang, Yuanjing Xu, Haijun Tian, Yuanqing Mao, Jinwu Wang, Zhiyuan Zhang
• Format: Article
• Language: English
• Published: BMC 2021-09-01
• Series: Journal of Nanobiotechnology
• Subjects: Metal-organic framework (MOF); Tumor hypoxia; Photothermal therapy (PTT); Osteosarcoma
• Online Access: https://doi.org/10.1186/s12951-021-01013-0

Abstract Background Hypoxia 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. Results The 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. Conclusions By 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