Tirapazamine-embedded polyplatinum(iv) complex: a prodrug combo for hypoxia-activated synergistic chemotherapy

• DOI: 10.1039/c9bm01640f
• Publication Date: 2019-11-15T04:23:32Z
• Authors: Dongbo Guo; Shuting Xu; Wumaier Yasen; Chuan Zhang; Jian Shen; Yu Huang; Dong Chen; Xinyuan Zhu
• Keywords: Tirapazamine; Hypoxia; Tumor Hypoxia

Despite the great advances achieved in hypoxia-associated tumor therapy, efficacy of hypoxia-activated prodrugs alone is usually limited owing to moderate oxygen supply at area. Herein, we develop a polymerized platinum(iv) compound-based nanogel (polyprodrug) containing bioreductive and prodrug (tirapazamine, TPZ) as combo (polyprodrug@TPZ) for synergistic chemotherapy. Upon exposure microenvironment, moieties polyprodrug are reduced platinum(ii) species, which significantly upregulates expression NADPH oxidases (NOXs) accelerate (O2) depletion promote reactive species (ROS) production, confirmed by reverse transcription-PCR (RT-PCR) fluorescence probes. In exaggerated hypoxia environment, highly cytotoxic radicals generated due TPZ activation, serve second antitumor agents working together with With rational design nanosized architecture, platinum(iv)-based polyprodrug@TPZ complex exhibits advantages redox-responsive drug release, superior accumulation, long-term circulation during treatment mouse model. These results indicate that combination an would promising strategy realize better