title: Efficacy Dependence of Photodynamic Therapy Mediated by Upconversion Nanoparticles: Subcellular Positioning and Irradiation Productivity.
abstract: Singlet oxygen (1O2), as an important kind of reactive oxygen species (ROS) and main therapeutic agent in photodynamic therapy (PDT), only have a half-life of 40 ns and an effective radius of 20 nm, which cause significant obstacles for improving PDT efficacy. In this work, novel upconversion nanoparticle (UCN)-based nanoplatforms are developed with a minimized distance between UCNs and a photosensitizer, protoporphyrin IX (PpIX), and a controllable payload of PpIX, to enhance and control ROS production. The ability of the nanoplatform to target different subcellular organelles such as cell membrane and mitochondria is demonstrated via surface modification of the nanoplatform with different targeting ligands. The results show that the mitochondria-targeting nanoplatforms result in significantly increased capability of both tumor cell killing and inhibition of tumor growth. Subcellular targeting of nanoparticles leads to the death of cancer cells in different manners. However, the efficiency of ROS generation almost have no influence on the tumor cell viability during the period of evaluation. These findings suggest that specific subcellular targeting of the nanoplatforms enhances the PDT efficacy more effectively than the increase of ROS production, and may shed light on future novel designs of effective and controllable PDT nanoplatforms.
authors.affiliation: State Key Lab of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Plastic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, P. R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.affiliation: State Key Lab of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tao
authors.affiliation: Department of Materials Science and Engineering, University of Sheffield, Mappin Street, Sheffield, S1 3JD, UK.
authors.forename: Biqiong
authors.initials: B
authors.lastname: Chen
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Seok Ki
authors.initials: SK
authors.lastname: Choi
authors.affiliation: State Key Lab of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai Stem Cell Institute, Shanghai, 200241, P. R. China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai Stem Cell Institute, Shanghai, 200241, P. R. China.
authors.forename: Guangdong
authors.initials: G
authors.lastname: Zhou
authors.affiliation: State Key Lab of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D011524:Protoporphyrins / Q000737:chemistry; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen / Q000494:pharmacology
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen; C028025:protoporphyrin IX
keywords: photodynamic therapy; reactive oxygen species; subcellular targeting; upconversion nanoparticles