Activity Control of Photosensitizers for Photodynamic Therapy through DNA Recognition

本研究的目的是对光动力疗法中的光敏剂的活性进行控制，光动力疗法是一种很有前途的癌症和一些非恶性疾病的治疗方法。只有当黄连素和巴马汀与DNA结合时，这些光敏剂才能使单线态氧的产生光敏。这项研究揭示了这些光敏剂活性控制的序列特异性，提示设计序列特异性光敏剂的可能性。为了将这种调控机制应用于临床使用的卟啉类光敏剂，我们合成了电子给体连接的卟啉化合物。这些卟啉的光激发态通过分子内电子转移猝灭。与DNA的相互作用抑制了这些光激发的卟啉的电子转移猝灭，导致光能转移到分子氧的单线态氧的产生。这些发现表明，可以利用电子给体连接卟啉来开发DNA选择性光敏剂。

The purpose of this study is the activity control of photosensitizers for photodynamic therapy, which is a promising treatment of cancer and some non-malignant conditions. Berberine and palmatine can photosensitize the generation of singlet oxygen only when these photosensitizers bind to DNA. This study revealed the sequence specificity on the activity control of these photosensitizers, suggesting the possibility of design of sequence-specific photosensitizer. To apply this control mechanism for clinical using porphyrinoid photosensitizer, the electron donor connecting porphyrins were synthesized. The photoexcited states of these porphyrins were quenched via intramolecular electron transfer. The interaction with DNA inhibited the electron transfer quenching of these photoexcited porphyrins, leading to the singlet oxygen generation via photoenergy transfer to molecular oxygen. These findings demonstrated that the DNA-selective photosensitizers can be developed using electron donor connecting porphyrins.