NF-?B hijacking theranostic Pt(ll) complex in cancer therapy.

ABSTRACT: Platinum complexes have been used for anti-cancer propose for decades, however, their high side effects resulting from damage to healthy cells cannot be neglected and prevent further clinical utilisation. Here, we designed a cyclometalated platinum (II) complex that can bind the endogenous nuclear factor-?B (NF-?B) protein. Employing detailed colocalization studies in co-culture cell line models, we show that by binding to NF-?B, the platinum (II) complex is capable of upregulated nuclear translocation specifically in cancer but not normal cells, thereby impairing cancer proliferation without disturbing healthy cells. In a murine tumour model, the platinum (II) complex prevents tumour growth to a greater extent than cisplatin and with considerably lower side-effects and kidney damage. Considering its weak damage to normal cells combined with high toxicity to cancer cells, this NF-?B-binding platinum complex is a potential anti-cancer candidate and acts to verify the strategy of hijacking endogenous trans-nuclear proteins to achieve cancer-cell specificity and enhance therapeutic indices.

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC6531303 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature