【摘要】 目的 研究新型二氢卟吩化合物5-(4-羧甲氧基苯基)-10,15,20-三苯基-二氢卟吩（D1）和5-(4-羧丙氧基苯基)-10,15,20-三苯基-二氢卟吩（D2）的光动力学性能及其介导的光动力学作用对肺癌的杀伤效果。方法 测定新化合物D1和D2的紫外-可见吸收光谱和荧光光谱；以1,3-二苯基异苯并呋喃（DPBF）作为单线态氧捕捉剂检测D1和D2的单线态氧生成能力；利用荧光法检测化合物在人肺腺癌细胞A549内的细胞吞噬率，用MTT法检测化合物的暗毒性和光毒性；建立肺癌荷瘤裸鼠模型，考察化合物介导的光动力作用在体内的抗肿瘤活性，并进一步检测D2在荷瘤裸鼠体内的血药浓度以及在肿瘤组织和皮肤组织中的分布。结果 D1和D2在652 nm长波长处具有强吸收，最佳激发波长位于429 nm和427 nm处，最佳发射波长位于659 nm左右，并具有高于对照药替莫泊芬（m-THPC）的单线态氧生成速率；D1和D2在10μmol/L以下的浓度基本没有暗毒性，并可被人肺腺癌细胞A549摄取，于18～24 h基本达到饱和；在650 nm波长激光照射后，D1和D2在体内外均具有明显的抗肿瘤活性（P<0.01），其中，化合物D2在给药后可选择性地聚集于肿瘤组织，最佳治疗时间为给药后30 min内。结论 D2具有优秀的光动力抗肿瘤活性，并能选择性聚集于肿瘤组织，具备成为肺癌诊治光敏剂候选药物的潜力，值得进一步的研究。更多还原

【Abstract】 Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-(4-(5,15,20-triphenyl-7H,8H-porphyrin-10-yl) phenoxy) acetic acid(D1)and 4-(4-(5,15,20-triphenyl-7H,8H-porphyrin-10-yl) phenoxy) butanoic acid(D2). Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18～24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro(P<0.01). However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues,which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.更多还原