Sun Jian-Da, Liu Yamin, Zhao Zijian, Yu Shang-Bo, Qi Qiao-Yan, Zhou Wei, Wang Hui, Hu Ke, Zhang Dan-Wei, Li Zhan-Ting
Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University 2205 Songhu Road Shanghai 200438 China
Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences 345 Lingling Lu Shanghai 200032 China
RSC Med Chem. 2023 Feb 7;14(3):563-572. doi: 10.1039/d2md00463a. eCollection 2023 Mar 22.
In the past two decades, photodynamic therapy (PDT) has become an effective method for the treatment of cancer. However, the posttreatment residue of photodynamic agents (PDAs) causes long-term skin phototoxicity. Here, we apply naphthalene-derived, box-like tetracationic cyclophanes, named NpBoxes, to bind to clinically used porphyrin-based PDAs to alleviate their posttreatment phototoxicity by reducing their free content in skin tissues and O quantum yield. We show that one of the cyclophanes, 2,6-NpBox, could include the PDAs to efficiently suppress their photosensitivity for the generation of reactive oxygen species. A tumour-bearing mouse model study revealed that, when Photofrin, the most widely used PDA in clinic, was administrated at a dose corresponding to the clinical one, 2,6-NpBox of the same dose could significantly suppress its posttreatment phototoxicity on the skin induced by simulated sunlight irradiation, without imposing a negative influence on its PDT efficacy.
在过去二十年中，光动力疗法（PDT）已成为治疗癌症的一种有效方法。然而，光动力剂（PDA）的治疗后残留会导致长期的皮肤光毒性。在此，我们应用萘衍生的盒状四价环番，即NpBoxes，与临床使用的基于卟啉的PDA结合，通过降低其在皮肤组织中的游离含量和单线态氧量子产率来减轻其治疗后的光毒性。我们表明，其中一种环番2,6-NpBox可以包合PDA，有效抑制其产生活性氧的光敏性。一项荷瘤小鼠模型研究表明，当以临床剂量施用临床上使用最广泛的PDA卟吩姆钠时，相同剂量的2,6-NpBox可以显著抑制模拟阳光照射诱导的其对皮肤的治疗后光毒性，而不会对其PDT疗效产生负面影响。
