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Photosensitizing effectiveness of a novel chlorin-based photosensitizer for photodynamic therapy in vitro and invivo

Zhang LJ, Bian J, Bao LL, Chen HF, Yan YJ, Wang L, Chen ZL.

J Cancer Res Clin Oncol. 2014;140(9):1527-36.

Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, People’s Republic of China.

 

Abstract

PURPOSE:

Photodynamic therapy (PDT) is a promising noninvasive treatment, which has been approved by the US Food and Drug Administration for the treatment of localized tumors. With the aim to select an appropriate photosensitizer for tumor treatment in PDT, the antitumor effect of anovel chlorin-based photosensitizer, meso-tetra (3-morphlinomethyl-4-methoxyphenyl) chlorin (TMMC) (Fig. 1a) on two types of human malignant tumor cells in vitro and a esophageal cancer model in nude mice, was evaluated in the present paper. Fig. 1 Chemical structure and spectrum properties of TMMC in DMF. a Chemical structure of TMMC in DMF. b UV-Vis absorption spectrum of TMMC in DMF. Its maximum absorbance is at 423 nm, and at 527, 555, 600, 655 nm and 712 nm, also it has absorption. c Emission spectrum of TMMC, which was excited at 514 nm, and its peaks were at 656 and 720 nm. d The matrix of excitation and emission spectra (Ex: 300-550 nm, Em: 600-780 nm)

METHODS:

The efficiency of TMMC-PDT in vitro was analyzed by MTT assay and clonogenic assay. The intracellular distribution of photosensitizers was detected with laser scanning confocal microscopy. The accumulation of TMMC in human malignant tumor cells was measured by Fluorescence Spectrometer, and the pathway of cell death was analyzed by flow cytometry. Eca-109 tumor model was used to evaluate the antitumor effects of TMMC-mediated PDT. And the singlet oxygen quantum yield of TMMC was also measured using DPBF as substrate.

RESULTS:

TMMC shows a singlet oxygen quantum yield of 0.59 and displays a characteristic long wavelength absorption peak at 655 nm. The accumulation of TMMC increased in time-dependent manner, and it was found in cytoplasm and nuclear membranes. TMMC-PDT induced cell death by the major death pathway of necrosis and significantly reduced the growth of Eca-109 tumors in nude mice (180 mW/cm(2), 120 J/cm(2)).

CONCLUSION:

The studies suggest that TMMC is an effective photosensitizer for PDT to tumors. Therefore, TMMC has great potentials for tumor treatment in PDT and deserves further investigation.

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Photodynamic Therapy