title: Hypoxia Induced by Upconversion-Based Photodynamic Therapy: Towards Highly Effective Synergistic Bioreductive Therapy in Tumors.
abstract: Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive pro-drugs that can be activated at low-oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica-shelled upconversion nanoparticles (UCNPs) nanostructure capable of co-delivering photosensitizer (PS) molecules and a bioreductive pro-drug (tirapazamine, TPZ) were designed (TPZ-UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC-based (UC-) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC-PDT. Treatment with TPZ-UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC-PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much-enhanced cytotoxicity of TPZ under PDT-induced hypoxia.
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-xi Road, Shanghai 200050 (P.R. China).
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, Shanghai Cancer Hospital, Fudan University, 270 Dong-an Road, Shanghai 200032 (P.R. China).
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-xi Road, Shanghai 200050 (P.R. China). wbbu@mail.sic.ac.cn.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Bu
authors.affiliation: Department of Nuclear Medicine, Changhai Hospital of Shanghai, 168 Chang-hai Road, Shanghai 200433 (P.R. China).
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Nuclear Medicine, Changhai Hospital of Shanghai, 168 Chang-hai Road, Shanghai 200433 (P.R. China).
authors.forename: Changjing
authors.initials: C
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-xi Road, Shanghai 200050 (P.R. China).
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Cancer Research Institute, Shanghai Cancer Hospital, Fudan University, 270 Dong-an Road, Shanghai 200032 (P.R. China).
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-xi Road, Shanghai 200050 (P.R. China).
authors.forename: Dalong
authors.initials: D
authors.lastname: Ni
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-xi Road, Shanghai 200050 (P.R. China).
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-xi Road, Shanghai 200050 (P.R. China).
authors.forename: Jianan
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-xi Road, Shanghai 200050 (P.R. China). jlshi@mail.sic.ac.cn.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Shi
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000378:metabolism*; D009369:Neoplasms / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*
chemical_list: D017319:Photosensitizing Agents
keywords: bioreductive pro-drugs; hypoxia; photodynamic therapy; synergetic therapy; upconversion nanoparticles