title: Corrosion-Activated Chemotherapeutic Function of Nanoparticulate Platinum as a Cisplatin Resistance-Overcoming Prodrug with Limited Autophagy Induction.
abstract: 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.
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35 Keyan Road, Zhunan, 35053, Taiwan.
authors.forename: Hsien-Jen
authors.initials: HJ
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35 Keyan Road, Zhunan, 35053, Taiwan.
authors.forename: Te-Haw
authors.initials: TH
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35 Keyan Road, Zhunan, 35053, Taiwan.
authors.forename: Chih-Te
authors.initials: CT
authors.lastname: Chien
authors.affiliation: National Synchrotron Radiation Research Center, No. 101, Hsin-Ann Road, Hsinchu, 30076, Taiwan.
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Tu
authors.affiliation: National Synchrotron Radiation Research Center, No. 101, Hsin-Ann Road, Hsinchu, 30076, Taiwan.
authors.forename: Ting-Shan
authors.initials: TS
authors.lastname: Cha
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35 Keyan Road, Zhunan, 35053, Taiwan.
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003343:Corrosion; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010087:Oxides / Q000494:pharmacology*; D056951:Photoelectron Spectroscopy; D010984:Platinum / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D056928:X-Ray Absorption Spectroscopy
chemical_list: D000970:Antineoplastic Agents; D010087:Oxides; D011355:Prodrugs; C514637:platinum oxide; D010984:Platinum; D002945:Cisplatin
keywords: autophagy; corrosion; drug resistance; enzyme mimetics; platinum nanoparticles