TY - JOUR
T1 - Effective Two-Photon Excited Photodynamic Therapy of Xenograft Tumors Sensitized by Water-Soluble Bis(arylidene)cycloalkanone Photosensitizers
AU - Zou, Qianli
AU - Zhao, Hongyou
AU - Zhao, Yuxia
AU - Fang, Yanyan
AU - Chen, Defu
AU - Ren, Jie
AU - Wang, Xiaopu
AU - Wang, Ying
AU - Gu, Ying
AU - Wu, Feipeng
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/9/23
Y1 - 2015/9/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84945357953&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.5b00731
DO - 10.1021/acs.jmedchem.5b00731
M3 - Article
C2 - 26397825
AN - SCOPUS:84945357953
SN - 0022-2623
VL - 58
SP - 7949
EP - 7958
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 20
ER -