Abstract
Chlorin derivatives are promising photosensitive agents for photodynamic therapy (PDT) of tumors. The aim of the current study is to investigate the PDT therapeutic effects of a novel chlorin-based photosensitizer, meso-tetra[3-(N,N-diethyl)aminomethyl-4-methoxy]phenyl chlorin (TMPC) for gliomas in vitro and in vivo. Physicochemical characteristics of TMPC were recorded by ultraviolet visible spectrophotometer and fluorescence spectrometer. The rate of singlet oxygen generation of TMPC upon photo-excitation was detected by using 1,3-diphenylisobenzofuran (DPBF). The accumulation of TMPC in gliomas U87 MG cells was measured by fluorescence spectrometer. The efficiency of TMPC-PDT in vitro was analyzed by MTT assay and clonogenic assay. The biodistribution and clearance of TMPC were determined by fluorescence measuring. Human gliomas U87 MG tumor-bearing mice model was used to evaluate the antitumor effects of TMPC-PDT. TMPC shows a singlet oxygen generation rate of 0.05 and displays a characteristic long wavelength absorption peak at 653 nm (ε = 15,400). The accumulation of TMPC increased with the increase of incubation time. In vitro, PDT using TMPC and laser showed laser dose- and concentration-dependent cytotoxicity to U87 MG cells. In U87 MG tumor-bearing mice, TMPC-PDT significantly reduced the growth of the tumors. Both in vitro and in vivo, TMPC showed little dark toxicity. In vitro and in vivo studies, it found that TMPC has excellent antitumor activities. It suggests that TMPC is a potential photosensitizer of photodynamic therapy for cancer.
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Acknowledgments
This work was supported by the Chinese National Natural Science Foundation (No. 21372042, 21402236, 81101298, 81301878), Foundation of Shanghai Government (No. 14431906200, 14140903500, 13431900700, 13430722300, 13ZR1441000, 13ZR1440900, 14ZR1439800, 14ZR1439900, 15ZR1439900, 15XD1523400, 14SJGGYY08, 201370), International Cooperation Foundation of China and Croatia (6-11), and Foundation of Yiwu Science and Technology Bureau (No. 2012-G3-02, 2013-G3-03).
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Wang, LX., Li, JW., Huang, JY. et al. Antitumor activity of photodynamic therapy with a chlorin derivative in vitro and in vivo. Tumor Biol. 36, 6839–6847 (2015). https://doi.org/10.1007/s13277-015-3395-1
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DOI: https://doi.org/10.1007/s13277-015-3395-1