Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, 264003, Shandong, PR China; Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, 999077, PR China.
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, 264003, Shandong, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
Eur J Med Chem. 2021 Jan 1;209:112867. doi: 10.1016/j.ejmech.2020.112867. Epub 2020 Sep 24.
Photodynamic therapy (PDT) is an emerging alternative cancer treatment modality that utilizes photo-sensitivity to cause cell death upon photo-irradiation. However, PDT efficiency has been hampered by tumor hypoxia, blue-shifted excitation wavelengths, and the high dark toxicity of photo-sensitizers. We designed and synthesized two novel porphycene-based photosensitizers (TBPoS-OH and TBPoS-2OH) with potent photo-cytotoxicity and a LD in the nM range under both normoxic and hypoxic conditions in a variety of cell types after photo-irradiation (λ = 640 ± 15 nm). Further studies showed fast-cellular uptake for TBPoS-OH that localized lysosomes and subsequently induced cell apoptosis via the lysosomal-mitochondrial pathway. Moreover, TBPoS-OH significantly reduced tumor growth in two xenografted mouse models bearing melanoma A375 and B16 cells. Finally, TBPoS-OH exhibited no obvious immunogenicity and toxicity to blood cells and major organs in mice. These data demonstrated that these two porphycene-based photosensitizers, especially TBPoS-OH, could be developed as a potential PDT modality.
光动力疗法（PDT）是一种新兴的癌症治疗方法，它利用光敏感性在光照射下引起细胞死亡。然而，PDT 的效率受到肿瘤缺氧、激发波长蓝移和光敏剂的高暗毒性的限制。我们设计并合成了两种新型卟啉类光敏剂（TBPoS-OH 和 TBPoS-2OH），它们在光照下具有强大的光细胞毒性和在纳米范围内的 LD，在多种细胞类型中，无论是在常氧还是缺氧条件下，激发波长为 640 ± 15nm。进一步的研究表明，TBPoS-OH 具有快速的细胞摄取能力，定位于溶酶体，并通过溶酶体-线粒体途径诱导细胞凋亡。此外，TBPoS-OH 显著抑制了携带黑色素瘤 A375 和 B16 细胞的两种异种移植小鼠模型中的肿瘤生长。最后，TBPoS-OH 对小鼠的血细胞和主要器官没有明显的免疫原性和毒性。这些数据表明，这两种基于卟啉的光敏剂，特别是 TBPoS-OH，可开发为一种潜在的 PDT 方法。
