A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor
| Autor: | Defang Li, Tao Han, Yao Qin, Xiao-Lan Cheng, Nai Ki Mak, Sam C. K. Hau, Kai Zhang, Minjing Li, Jun Lu, Guowei Deng, Zhaohai Pan, Daniel W. J. Kwong, Kwok Keung Shiu, Xin Zhang, Jiaojiao Fan, Wang Yuzhi, Ting Yan, Qiusheng Zheng, Xiaona Liu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Models Molecular Cell type Programmed cell death Porphyrins genetic structures Light medicine.medical_treatment Photodynamic therapy Apoptosis Crystallography X-Ray 01 natural sciences 03 medical and health sciences Mice Drug Discovery medicine Animals Humans Melanoma 030304 developmental biology Pharmacology 0303 health sciences Mice Inbred BALB C Sulfonamides Photosensitizing Agents Tumor hypoxia 010405 organic chemistry Chemistry Immunogenicity Organic Chemistry General Medicine medicine.disease 0104 chemical sciences Photochemotherapy Toxicity Cancer research Tumor Hypoxia |
| Zdroj: | European journal of medicinal chemistry. 209 |
| ISSN: | 1768-3254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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