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

摘要

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 a novel 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. 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/cm2, 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.