Chemistry Research Unit (CIQUP), Faculty of Sciences of University of Porto (FCUP), Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
LACOMEPHI, GreenUPorto, Faculty of Sciences of University of Porto (FCUP), Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
Biomolecules. 2019 Aug 20;9(8):384. doi: 10.3390/biom9080384.
Cancer is a very challenging disease to treat, both in terms of treatment efficiency and side-effects. To overcome these problems, there have been extensive studies regarding the possibility of improving treatment by employing combination therapy, and by exploring therapeutic modalities with reduced side-effects (such as photodynamic therapy (PDT)). Herein, this work has two aims: (i) to develop self-activating photosensitizers for use in light-free photodynamic therapy, which would eliminate light-related restrictions that this therapy currently possesses; (ii) to assess their co-treatment potential when combined with reference chemotherapeutic agents (Tamoxifen and Metformin). We synthesized three new photosensitizers capable of self-activation and singlet oxygen production via a chemiluminescent reaction involving only a cancer marker and without requiring a light source. Cytotoxicity assays demonstrated the cytotoxic activity of all photosensitizers for prostate and breast tumor cell lines. Analysis of co-treatment effects revealed significant improvements for breast cancer, producing better results for all combinations than just for the individual photosensitizers and even Tamoxifen. By its turn, co-treatment for prostate cancer only presented better results for one combination than for just the isolated photosensitizers and Metformin. Nevertheless, it should be noted that the cytotoxicity of the isolated photosensitizers in prostate tumor cells was already very appreciable.
癌症是一种极具挑战性的疾病，无论是在治疗效率还是副作用方面。为了克服这些问题，人们广泛研究了通过联合治疗来提高治疗效果的可能性，并探索了副作用较小的治疗方式（如光动力疗法（PDT））。在此，这项工作有两个目标：（i）开发用于无光照光动力治疗的自激活光敏剂，以消除该疗法目前存在的与光照相关的限制；（ii）评估它们与参考化疗药物（他莫昔芬和二甲双胍）联合使用的协同治疗潜力。我们合成了三种新的光敏剂，它们能够通过涉及仅癌症标志物且不需要光源的化学发光反应进行自激活和单线态氧的产生。细胞毒性试验表明，所有光敏剂对前列腺和乳腺癌肿瘤细胞系均具有细胞毒性活性。联合治疗效果分析显示，对乳腺癌有显著改善作用，所有组合的效果均优于单一光敏剂甚至他莫昔芬。相比之下，对于前列腺癌，只有一种组合的联合治疗效果优于单一光敏剂和二甲双胍。然而，值得注意的是，在前列腺肿瘤细胞中，单一光敏剂的细胞毒性已经非常显著。
