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Cao, Qian; Zhou, Dan‐Jie; Pan, Zheng‐Yin; Yang, Gang‐Gang; Zhang, Hang; Ji, Liang‐Nian; Mao, Zong‐Wan
Angewandte Chemie (International ed.), October 12, 2020, Letnik: 59, Številka: 42Journal Article
Hypoxia and the acidic microenvironment play a vital role in tumor metastasis and angiogenesis, generally compromising the chemotherapeutic efficacy. This provides a tantalizing angle for the design of platinum(IV) prodrugs for the effective and selective killing of solid tumors. Herein, two carbonic anhydrase IX (CAIX)‐targeting platinum(IV) prodrugs have been developed, named as CAIXplatins. Based on their strong affinity for and inhibition of CAIX, CAIXplatins can not only overcome hypoxia and the acidic microenvironment, but also inhibit metabolic pathways of hypoxic cancer cells, resulting in a significantly enhanced therapeutic effect on hypoxic MDA‐MB‐231 tumors both in vitro and in vivo compared with cisplatin/oxaliplatin, accompanied with excellent anti‐metastasis and anti‐angiogenesis activities. Furthermore, the cancer selectivity indexes of CAIXplatins are 70–90 times higher than those of cisplatin/oxaliplatin with effectively alleviated side‐effects. Tumor microenvironment and metabolism regulation can be achieved by targeting carbonic anhydrase IX with platinum(IV) prodrugs, termed CAIXplatins. This strategy could be used to treat hypoxic and aggressive tumors. The advantages of CAIXplatins in comparison to cisplatin/oxaliplatin include the greatly increased cancer selectivity index, enhanced therapeutic efficiency, reduced level of side‐effects, as well as the excellent anti‐angiogenesis activity.
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