title: A Smart Photosensitizer-Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells.
abstract: Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer-MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery.
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Fan
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.
authors.forename: Guobei
authors.initials: G
authors.lastname: Yan
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.|Department of Chemistry and Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, FL, 32611-7200, USA.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Fu
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Fu
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China. xbzhang@hnu.edu.cn.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Zhang
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China. tan@chem.ufl.edu.|Department of Chemistry and Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, FL, 32611-7200, USA. tan@chem.ufl.edu.
authors.forename: Weihong
authors.initials: W
authors.lastname: Tan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002735:Chlorophyllides; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D017895:Manganese Compounds / Q000737:chemistry / Q000378:metabolism*; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry; D010084:Oxidation-Reduction; D010087:Oxides / Q000737:chemistry / Q000378:metabolism*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D011166:Porphyrins / Q000008:administration & dosage* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002735:Chlorophyllides; D003692:Delayed-Action Preparations; D017895:Manganese Compounds; D010087:Oxides; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C062985:phytochlorin; D005978:Glutathione; C016552:manganese dioxide
keywords: MnO2 nanosheets; cancer cells; glutathione; photodynamic therapy; singlet oxygen