title: Effective Two-Photon Excited Photodynamic Therapy of Xenograft Tumors Sensitized by Water-Soluble Bis(arylidene)cycloalkanone Photosensitizers.
abstract: A series of bis(arylidene)cycloalkanone photosensitizers modified by polyethylene glycol (PEG) have been studied for two-photon excited photodynamic therapy (2PE-PDT). As compared with their prototype compounds, these PEGylated photosensitizers show enhanced water solubilities while their photophysical and photochemical properties, including linear absorption, two-photon absorption, fluorescence, and singlet oxygen quantum yield, remain unaltered. In vitro behaviors (cellular uptake, subcellular localization, photocytotoxicity in both PDT and 2PE-PDT) of these photosensitizers reveal that an optimized lipid-water partition coefficient can be obtained by adjusting the length and position of the PEG chains. Among them, the photosensitizer modified asymmetrically by two tetraethylene glycol chains presents the best performance as a 2PE-PDT candidate. Selective blood-vessel closure and obvious therapeutic effect in inhibiting the growth of tumors are confirmed by in vivo 2PE-PDT after intravenous injection of this photosensitiezer. The survival periods of treated tumor-bearing mice are significantly prolonged. This study demonstrates the feasibility of using a simple molecule to construct a potential candidate for 2PE-PDT.
authors.affiliation: Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , 29 Zhongguancun East Road, Beijing 100190, P. R. China.|Institute of Process Engineering, National Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences , Beijing 100190, P. R. China.
authors.forename: Qianli
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital , Beijing 100853, P. R. China.
authors.forename: Hongyou
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , 29 Zhongguancun East Road, Beijing 100190, P. R. China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , 29 Zhongguancun East Road, Beijing 100190, P. R. China.|University of Chinese Academy of Sciences , Beijing 100049, P. R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital , Beijing 100853, P. R. China.
authors.forename: Defu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital , Beijing 100853, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , 29 Zhongguancun East Road, Beijing 100190, P. R. China.|University of Chinese Academy of Sciences , Beijing 100049, P. R. China.
authors.forename: Xiaopu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital , Beijing 100853, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital , Beijing 100853, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , 29 Zhongguancun East Road, Beijing 100190, P. R. China.
authors.forename: Feipeng
authors.initials: F
authors.lastname: Wu
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000628:therapy; D010100:Oxygen / Q000737:chemistry; D010778:Photochemotherapy / Q000379:methods*; D017785:Photons; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry; D012510:Sarcoma 180 / Q000188:drug therapy / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D023041:Xenograft Model Antitumor Assays
chemical_list: D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols; D010100:Oxygen