A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY(2021)
摘要
Photodynamic therapy (PDT) is an emerging alternative cancer treatment modality that utilizes photosensitivity 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 (lambda = 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. (c) 2020 Elsevier Masson SAS. All rights reserved.
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关键词
Photodynamic therapy,Porphycene,Hypoxic,Tumor,Melanoma
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