101. Effective Two-Photon Excited Photodynamic Therapy of Xenograft Tumors Sensitized by Water-Soluble Bis(arylidene)cycloalkanone Photosensitizers
- Author
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Hongyou Zhao, Yanyan Fang, Ying Gu, Feipeng Wu, Defu Chen, Ying Wang, Qianli Zou, Xiaopu Wang, Yuxia Zhao, and Jie Ren
- Subjects
medicine.medical_treatment ,Quantum yield ,Photodynamic therapy ,Polyethylene glycol ,Photochemistry ,Polyethylene Glycols ,Mice ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Drug Discovery ,PEG ratio ,medicine ,Animals ,Humans ,Photosensitizer ,Sarcoma 180 ,Mice, Inbred BALB C ,Photons ,Photosensitizing Agents ,Singlet oxygen ,Neoplasms, Experimental ,Xenograft Model Antitumor Assays ,Fluorescence ,Oxygen ,Spectrometry, Fluorescence ,Photochemotherapy ,chemistry ,Injections, Intravenous ,Blood Vessels ,Molecular Medicine ,Female ,Reactive Oxygen Species - 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.
- Published
- 2015
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