The formation of intracellular nanoparticles correlates with cisplatin resistance

Meng Cao1,2,*, Fangzhou Liu1,3,4,*, Xiquan Zhang1,5,*, Ming Zheng6, Ziqi Ye1,7,*, Weiwei Chang1,5,*, Min Ji1,*, Xi Zhan8,1,*, Ning Gu1,1,*,*
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  • AcceptedJul 15, 2015
  • PublishedAug 31, 2015


Patients treated with the cisplatin often develop strong resistance to the drug after prolonged treatments, ultimately resulting in limited clinical efficacy. One of the possible mechanisms is that the internalized compound may be inactivated before getting access to the nucleus where cisplatin forms a complex with the genomic DNA and triggers a cell death program. However, the nature and intracellular fate of inactivated cisplatin is poorly illustrated. In the present study, we reported for the first time the presence of platinum nanoparticles (Pt-NPs) in the cytoplasm of cells treated with cisplatin. Further analysis also evidenced a correlation of the increased intracellular Pt- NPs formation with cisplatin resistance, and confirmed the process was glutathione S-transferase relevant. Our data suggest that tumor cells may develop cisplatin resistance by converting the drug into less toxic intracellular Pt-NPs, thereby impeding the drug from targeting its substrates.


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