title: An upconversion nanoplatform for simultaneous photodynamic therapy and Pt chemotherapy to combat cisplatin resistance.
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) [NaGdF4:Yb/Nd@NaGdF4:Yb/Er@NaGdF4] that were covalently loaded with not only photosensitizers (PSs), but also Pt(iv) prodrugs, which were rose bengal (RB) and c,c,t-[Pt(NH3)2Cl2(OCOCH2CH2NH2)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.
authors.affiliation: 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.
authors.forename: Fujin
authors.initials: F
authors.lastname: Ai
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong SAR.
authors.forename: Tianying
authors.initials: T
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Zoufeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong SAR.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR. guangzhu@cityu.edu.hk.
authors.forename: Man Wai
authors.initials: MW
authors.lastname: To
authors.affiliation: 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003959:Diamines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008027:Light; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010778:Photochemotherapy; D010984:Platinum / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012395:Rose Bengal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003959:Diamines; D011355:Prodrugs; D017382:Reactive Oxygen Species; D012395:Rose Bengal; D011092:Polyethylene Glycols; D010984:Platinum; D002945:Cisplatin; C007297:1,6-diaminohexane