Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Science, Nagoya, Japan;
Anticancer Res. 2024 Mar;44(3):1011-1021. doi: 10.21873/anticanres.16896.
BACKGROUND/AIM: Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light, causing a photochemical reaction that releases free radicals, thereby inducing tumor cell necrosis via oxidative stress. The oxygen molecule reaches the singlet excited state through efficient energy transfer from an excited triplet state of the photosensitizer. Heavy atoms are frequently introduced in photosensitizers for efficiently generating reactive oxygen species (ROS) in PDT, known as the heavy atom effect. However, metal-complexed photosensitizers often show low water-solubility. To overcome this limitation and produce ROS effectively, we focused on the better solubility of photosensitizers with heavy metals bound within the chlorin skeleton and conjugated with glucose in this study.
We established maltotriose (Mal)-conjugation with heavy metallochlorins [M (Mal-chlorin), M=Pt or Pd)] and evaluated its anti-tumor effect.
M (Mal-chlorin) showed effective ROS production and singlet oxygen induction. Consequently, these cytotoxic factors caused effective anti-tumor effects and induced morphological changes, followed by cell death in vitro. In a xenograft tumor mouse model, PDT with M (Mal-chlorin) showed tumor growth suppression.
M (Mal-Chlorin) might be an excellent glucose-conjugated chlorin because of its strong anti-tumor PDT effect.
背景/目的：光动力疗法（PDT）是一种相对非侵入性的抗癌疗法，它使用具有特定波长的光敏剂，引发光化学反应释放自由基，通过氧化应激诱导肿瘤细胞坏死。氧分子通过从光敏剂的激发三重态到单线态的有效能量转移到达单线激发态。为了在 PDT 中有效地生成活性氧（ROS），通常会在光敏剂中引入重原子，这被称为重原子效应。然而，金属配合的光敏剂通常表现出低水溶性。为了克服这一限制并有效地产生 ROS，我们专注于将结合重金属的卟啉类光敏剂与葡萄糖结合，以提高其在水中的溶解度。
我们用麦芽三糖（Mal）对重金属卟啉[M（Mal-卟啉），M=Pt 或 Pd]进行了偶联，并评估了其抗肿瘤效果。
M（Mal-卟啉）显示出有效的 ROS 生成和单线态氧诱导能力。因此，这些细胞毒性因子在体外导致了有效的抗肿瘤作用，并诱导了形态变化，随后导致细胞死亡。在异种移植肿瘤小鼠模型中，M（Mal-卟啉）的 PDT 显示出肿瘤生长抑制作用。
M（Mal-卟啉）可能是一种优秀的葡萄糖结合卟啉，因为它具有强大的抗肿瘤 PDT 效果。
