期刊
JOURNAL OF NANOBIOTECHNOLOGY
卷 19, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12951-021-01013-0
关键词
Metal-organic framework (MOF); Tumor hypoxia; Photothermal therapy (PTT); Osteosarcoma
资金
- National Key R&D Program of China [2018YFB 1105600/2018YFA0703000]
- National Natural Science Foundation of China [82072412/81772326]
- Project of Shanghai Science and Technology Commission [19XD1434200/18431903700]
- Two-hundred Talent Support [20152224]
- National infrastructures for translational medicine (Shanghai) open grant [TMSK-2020-120]
This study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with photothermal therapy, the growth of osteosarcoma xenografts can be effectively inhibited.
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-1 alpha 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-1 alpha 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.
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