超分子化学
材料科学
顺铂
铂金
癌细胞
立体化学
癌症研究
组合化学
癌症
生物
分子
生物化学
化疗
催化作用
有机化学
化学
遗传学
作者
Xidong He,Jie Yu,Renyong Yin,Peng Zhang,Chunsheng Xiao,Xuesi Chen
标识
DOI:10.1002/adma.202312488
摘要
Drug resistance significantly hampers the clinical application of existing platinum-based anticancer drugs. New platinum medications that possess distinct mechanisms of action are highly desired for the treatment of Pt-resistant cancers. Herein, a nanoscale trans-platinum(II)-based supramolecular coordination self-assembly (Pt-TCPP-BA) is prepared via using trans-[PtCl2 (pyridine)(NH3 )] (transpyroplatin), tetracarboxylporphyrin (TCPP), and benzoic acid (BA) as building blocks to combat drug resistance in platinum-based chemotherapy. Mechanistic studies indicate that Pt-TCPP-BA shows a hydrogen-peroxide-responsive dissociation behavior along with the generation of bioactive trans-Pt(II) and TCPP-Pt species. Different from cisplatin, these degradation products interact with DNA via interstrand cross-links and small groove binding, and induce significant upregulation of cell-death-related proteins such as p53, cleaved caspase 3, p21, and phosphorylated H2A histone family member X in cisplatin-resistant cancer cells. As a result, Pt-TCPP-BA exhibits potent killing effects against Pt-resistant tumors both in vitro and in vivo. Overall, this work not only provides a new platinum drug for combating drug-resistant cancer but also offers a new paradigm for the development of platinum-based supramolecular anticancer drugs.
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