Journal of Photochemistry and Photobiology B: Biology ( IF 5.4 ) Pub Date : 2020-09-05 , DOI: 10.1016/j.jphotobiol.2020.112015 Yi Dong 1 , Guangzhe Li 2 , Liu Wang 1 , Lei Cao 1 , Yueqing Li 2 , Weijie Zhao 2
Photodynamic therapy (PDT) is a non-invasive and innovative therapeutic approach which has been increasingly applied in clinical cancer therapy. As the central element of PDT, the development of novel photosensitizers (PSs) with longer absorption wavelength, proper lipophilic/hydrophilic profiles, target tissue selectivity, and higher photo−/lowest dark-cytotoxicity is a challenging task. Previously, we designed and synthesized a series of novel long-wavelength chlorin e6 (Ce6)-based PSs via introducing aromatic groups to the vinyl of Ce6 skeleton. The new formed compounds with π-extension system exhibited improved photodynamic effects and spectral characteristics. Among these π-conjugated chlorin PSs, (E)-32-(4-methoxyphenyl)-chlorin e6, named A15, was expected to be a potent antitumor candidate as a PDT agent due to its good photobiological properties. Herein, in this work, we evaluated the effectiveness of A15 in cancer PDT. In vitro, a novel rare earth probe, ATTA-Eu3+ was applied to detect the singlet oxygen (1O2) production of A15 in solution and human hepatoma HepG2 cells, respectively. Moreover, A15 exhibited strong phototoxicity and weak dark cytotoxity to HepG2 cells. In H22 tumor bearing mice, A15 showed excellent tumor accumulation ability via i.v. administration and induced tumor regression, followed by laser treatment. These results indicated that A15 is a potential novel π–extension chlorin-type PS for PDT applications.
中文翻译:
新型甲氧基苯基取代二氢卟酚光敏剂的抗肿瘤评价,用于光动力治疗。
光动力疗法(PDT)是一种非侵入性的创新治疗方法,已越来越多地应用于临床癌症治疗。作为PDT的核心元素,开发具有更长吸收波长,合适的亲脂性/亲水性,目标组织选择性以及更高的光/最低暗细胞毒性的新型光敏剂(PSs)是一项艰巨的任务。以前,我们通过将芳族基团引入Ce6骨架的乙烯基,设计并合成了一系列新型的基于长波长二氢卟吩e6(Ce6)的PS 。具有π-延伸体系的新形成的化合物表现出改善的光动力效应和光谱特性。在这些π共轭二氢卟酚PS中,(E)-3 2-(4-甲氧基苯基)-二氢卟酚e6,称为A15由于其良好的光生物学特性,有望被用作PDT的有效抗肿瘤药物。本文中,我们在这项工作中评估了A15在癌症PDT中的有效性。在体外,一种新颖的稀土探针ATTA-Eu 3+被应用于检测溶液和人肝癌HepG2细胞中A15的单线态氧(1 O 2)产生。而且,A15对HepG2细胞表现出强的光毒性和弱的暗细胞毒性。在荷H22荷瘤小鼠中,A15通过静脉注射显示出优异的肿瘤蓄积能力给药并诱导肿瘤消退,然后进行激光治疗。这些结果表明,A15是用于PDT应用的潜在的新型π扩展二氢卟酚型PS。