NDLI: An upconversion nanoplatform for simultaneous photodynamic therapy and Part chemotherapy to combat cisplatin resistance

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sun, Tianying Kong, Wei Xu, Zoufeng To, Man Wai Wang, Zhigang Ai, Fujin Wang, Feng Zhu, Guangyu
Description	Author Affiliation: Ai F ( Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR. guangzhu@cityu.edu.hk and City University of Hong Kong Shenzhen Research Institute, Shenzhen, P. R. China.); Sun T ( Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong SAR.); Xu Z ( Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR. guangzhu@cityu.edu.hk and City University of Hong Kong Shenzhen Research Institute, Shenzhen, P. R. China.); Wang Z ( Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR. guangzhu@cityu.edu.hk and City University of Hong Kong Shenzhen Research Institute, Shenzhen, P. R. China.); Kong W ( Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong SAR.); To MW ( Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR. guangzhu@cityu.edu.hk.); Wang F ( Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong SAR and City University of Hong Kong Shenzhen Research Institute, Shenzhen, P. R. China.); Zhu G ( Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR. guangzhu@cityu.edu.hk and City University of Hong Kong Shenzhen Research Institute, Shenzhen, P. R. China.)
Abstract	Platinum-based antineoplastic drugs are among the first-line chemotherapeutic agents against a variety of solid tumors, but toxic side-effects and drug resistance issues limit their clinical optimization. Novel strategies and platforms to conquer cisplatin resistance are highly desired. Herein, we assembled a multimodal nanoplatform utilizing 808 nm-excited and biocompatible core–shell–shell upconversion nanoparticles (UCNPs) $[NaGdF_{4}:Yb/Nd@NaGdF_{4}:Yb/Er@NaGdF_{4}]$ that were covalently loaded with not only photosensitizers (PSs), but also Pt(IV) prodrugs, which were rose bengal (RB) and $c,c,t-[Pt(NH_{3})_{2}Cl_{2}(OCOCH_{2}CH_{2}NH_{2})_{2}],$ respectively. The UCNPs had the capability to convert near infrared (NIR) light to visible light, which was further utilized by RB to generate singlet oxygen. At the same time, the nanoplatform delivered the Pt(IV) prodrug into cancer cells. Thus, this upconversion nanoplatform was able to carry out combined and simultaneous photodynamic therapy (PDT) and Pt chemotherapy. The nanoplatform was well characterized and the energy transfer efficiency was confirmed. Compared with free cisplatin or UCNPs loaded with RB only, our nanoplatform showed significantly improved cytotoxicity upon 808 nm irradiation in both cisplatin-sensitive and -resistant human ovarian cancer cells. A mechanistic study showed that the nanoparticles efficiently delivered the Pt(IV) prodrug into cancer cells, resulting in Pt-DNA damage, and that the nanoplatform generated cellular singlet oxygen to kill cancer cells. We, therefore, provide a comprehensive strategy to use UCNPs for combined Pt chemotherapy and PDT against cisplatin resistance, and our nanoplatform can also be used as a theranostic tool due to its NIR bioimaging capacity.
ISSN	14779226
Issue Number	33
Journal	Dalton Trans.
Volume Number	45
e-ISSN	13645447
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2016-08-16
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Chemistry
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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