tirapazamine and Osteosarcoma

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.. 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.. 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.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Fluorocarbons; Humans; Indoles; Male; Metal-Organic Frameworks; Mice; Mice, Nude; Nanoparticles; Osteosarcoma; Phthalic Acids; Polymers; Tirapazamine; Tumor Hypoxia

Topics: Amino Acid Transport System y+; Antineoplastic Agents; Bone Neoplasms; Cell Line, Tumor; Ferroptosis; Humans; Osteosarcoma; Tirapazamine