A Nanoscale Trans-Platinum(II)-Based Supramolecular Coordination Self-Assembly with a Distinct Anticancer Mechanism

被引：7

作者：

He, Xidong ^{[1
,2
]}

Yu, Jie ^{[1
,2
]}

Yin, Renyong ^{[1
,2
]}

Zhang, Peng ^{[1
,2
]}

Xiao, Chunsheng ^{[1
,2
]}

Chen, Xuesi ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Key Lab Polymer Ecomat, Jilin Biomed Polymers Engn Lab, Changchun Inst Appl Chem, Changchun 130022, Peoples R China

[2] Univ Sci & Technol China, Sch Appl Chem & Engn, Hefei 230026, Peoples R China

来源：

ADVANCED MATERIALS | 2024年 / 36卷 / 19期

基金：

中国国家自然科学基金;

关键词：

cancer therapy; drug resistance; nanomedicine; platinum drug; supramolecular self-assembly; MOLECULAR-MECHANISMS; PHOTODYNAMIC THERAPY; ORGANIC FRAMEWORKS; DNA INTERACTIONS; CELL-CYCLE; COMPLEXES; CISPLATIN; CANCER; POLYMERS; OXYGEN;

D O I：

10.1002/adma.202312488

中图分类号：

O6 [化学];

学科分类号：

0703 ;

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.

引用

页数：13

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