title: A New Approach to Sensitize Antitumor Monofunctional Platinum(II) Complexes via Short Time Photo-Irradiation.
abstract: Sensitizing the antitumor activity of monofunctional PtIIcomplexes is a reliable approach to developing antitumor agents different from the classic Pt-based drugs. Considering the poor intracellular accumulation of monofunctional PtIIcomplexes, in this study, the photosensitizing monofunctional PtIIcomplex Pt-BA was derived from a weak BODIPY (boron-dipyrromethene)-derived photosensitizer BA, with the purpose to improve its antitumor cytotoxicity via enhancing its intracellular accumulation with a short time photo-irradiation. Photoinduced reactive oxygen species (ROS) determination indicated that the PtIIcenter in Pt-BA is able to improve the photoinduced ROS production ability of BA, which makes Pt-BA a mild photosensitizer. Fluorescence imaging disclosed that dark incubation makes Pt-BA accumulate mainly on the surface of cell membrane, and the later short time photo-irradiation (5 min) promotes distinctly the intracellular accumulation of Pt-BA, which has been confirmed by inductively coupled plasma-mass spectrometry determination. Flow cytometric Annexin V-FITC assay indicated that the short time irradiation of Pt-BA induces in situ the cell membrane damage, which might finally enhance the intracellular accumulation of this monofunctional complex. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay confirmed that the short time photo-irradiation promotes distinctly the antitumor cytotoxicity of Pt-BA against MCF-7, SGC-7901, A549, and HeLa cell lines. The photopromoted antitumor activity of Pt-BA implies that modifying monofunctional PtIIcomplex as a mild photosensitizer to promote its cell accumulation is a useful approach to sensitizing the antitumor activity of monofunctional PtIIcomplex and renders the possibility of monofunctional PtIIprodrugs for precise chemotherapy via only short time photoactivation.
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Xuling
authors.initials: X
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Huachao
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Xiangchao
authors.initials: X
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Weijiang
authors.identifier: http://orcid.org/0000-0002-3157-5769
authors.initials: W
authors.lastname: He
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D005453:Fluorescence; D006801:Humans; D008027:Light; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D017382:Reactive Oxygen Species
chemical_list: D000970:Antineoplastic Agents; D001896:Boron Compounds; D009944:Organoplatinum Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species