Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, People's Republic of China.
J Cancer Res Clin Oncol. 2014 Sep;140(9):1527-36. doi: 10.1007/s00432-014-1717-0. Epub 2014 May 27.
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. 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.
目的：光动力疗法（PDT）是一种有前途的非侵入性治疗方法，已获得美国食品和药物管理局批准用于治疗局部肿瘤。本研究旨在选择一种合适的光敏剂用于 PDT 中的肿瘤治疗，评估了新型氯代啉类光敏剂间-四（3-吗啉基-4-甲氧基苯基）氯代啉（TMMC）（图 1a）对两种体外人恶性肿瘤细胞和裸鼠食管癌模型的抗肿瘤作用。
图 1 TMMC 在 DMF 中的化学结构和光谱性质。a TMMC 在 DMF 中的化学结构。b TMMC 在 DMF 中的紫外-可见吸收光谱。其最大吸收波长在 423nm，在 527、555、600、655nm 和 712nm 处也有吸收。c TMMC 的发射光谱，在 514nm 激发，其峰在 656nm 和 720nm。d 激发和发射光谱的基质（Ex：300-550nm，Em：600-780nm）
方法：通过 MTT 测定和集落形成试验分析 TMMC-PDT 的体外效率。用激光共聚焦显微镜检测光敏剂的细胞内分布。用荧光分光光度计测定 TMMC 在人恶性肿瘤细胞中的积累，用流式细胞术分析细胞死亡途径。用 Eca-109 肿瘤模型评价 TMMC 介导的 PDT 的抗肿瘤作用，并以 DPBF 为底物测定 TMMC 的单线态氧量子产率。
结果：TMMC 的单线态氧量子产率为 0.59，在 655nm 处显示出特征的长波长吸收峰。TMMC 的积累随时间呈时间依赖性增加，存在于细胞质和核膜中。TMMC-PDT 通过坏死的主要死亡途径诱导细胞死亡，并显著抑制裸鼠 Eca-109 肿瘤的生长（180mW/cm(2)，120J/cm(2)）。
结论：研究表明 TMMC 是一种有效的 PDT 肿瘤光敏剂。因此，TMMC 在 PDT 中具有治疗肿瘤的巨大潜力，值得进一步研究。
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