Carbon monoxide (CO)-Strengthened cooperative bioreductive anti-tumor therapy via mitochondrial exhaustion and hypoxia induction. (July 2019)

• Record Type: Journal Article
• Authors: Li, Yongjuan; Dang, Juanjuan; Liang, Qiujun; Yin, Lichen
• Is Part Of: Biomaterials. Volume 209(2019)
• Page Start: 138
• Page End: 151
• Publication Date: 2019-07
• Subjects: Carbon monoxide (CO) -- Bioreductive drug -- Mitochondrial metabolism -- Hypoxia responsiveness -- Anti-cancer therapy; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2019.04.004
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Bioreductive chemodrugs require hypoxic conditions to activate their anti-cancer efficacy. The insufficient and heterogeneous hypoxic condition in tumor tissues hurdles the therapeutic potency of bioreductive chemodrugs. We herein report a NIR light-triggered CO release system based on mesoporous Prussian blue nanoparticles (PB NPs) to enable cancer-selective hypoxia aggravation and hypoxia-responsive activation of bioreductive anti-cancer drug, tirapazamine (TPZ). Pentacarbonyl iron (Fe(CO)5 ) was coupled to PB NPs via coordination interaction, and TPZ was encapsulated into the pores of PB NPs. To prolong blood circulation and improve tumor accumulation, the PB-CO-TPZ NPs were surface-decorated with PEG-NH2 . Upon tumor site-specific light irradiation, the non-lethal photothermal effect of PB NPs released CO, which accelerated mitochondrial oxygen consumption and generated hypoxia to activate TPZ. The CO-induced mitochondrial exhaustion simultaneously led to cancer cell apoptosis, thus realizing synergistic anti-cancer effect with TPZ-mediated bioreductive chemotherapy. To the best of our knowledge, it is the first time to activate bioreductive chemotherapy using CO. This study thus provides a promising paradigm to realize effective and safe cancer treatment via precise manipulation of drug activities, and may open new insights in the use of CO for biomedical treatment.