Journal
SMALL
Volume 12, Issue 44, Pages 6124-6133Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201602374
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Funding
- National Health Research Institutes of Taiwan [NHRI-BN-104-PP-30/32]
- Ministry of Science and Technology of Taiwan [MOST-103-2325-B-400-014, MOST-104-2325-B-400-004]
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Despite nanoparticulate platinum (nano-Pt) has been validated to be acting as a platinum-based prodrug for anticancer therapy, the key factor in controlling its cytotoxicity remains to be clarified. In this study, it is found that the corrosion susceptibility of nano-Pt can be triggered by inducing the oxidization of superficial Pt atoms, which can kill both cisplatin-sensitive/resistance cancer cells. Direct evidence in the oxidization of superficial Pt atoms is validated to observe the formation of platinum oxides by X-ray absorption spectroscopy. The cytotoxicity is originated from the dissolution of nano-Pt followed by the release of highly toxic Pt ions during the corrosion process. Additionally, the limiting autophagy induction by nano-Pt might prevent cancer cells from acquiring autophagy-related drug resistance. With such advantages, the possibility of further autophagy-related drug resistance could be substantially reduced or even eliminated in cancer cells treated with nano-Pt. Moreover, nano-Pt is demonstrated to kill cisplatin-resistant cancer cells not only by inducing apoptosis but also by inducing necrosis for pro-inflammatory/inflammatory responses. Thus, nano-Pt treatment might bring additional therapeutic benefits by regulating immunological responses in tumor microenvironment. These findings support the idea that utilizing nano-Pt for its cytotoxic effects might potentially benefit patients with cisplatin resistance in clinical chemotherapy.
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