A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor
Yuzhi Wang1, Zhaohai Pan2, Xiao-Lan Cheng3
1Yantai 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.
Abstract:
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 LD50 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.
