A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor

Yuzhi Wang, Zhaohai Pan, Xiao Lan Cheng, Kai Zhang, Xin Zhang, Yao Qin, Jiaojiao Fan, Ting Yan, Tao Han, Kwok Keung SHIU, Sam C K HAU, Nai Ki MAK, Daniel W J KWONG, Xiaona Liu, Minjing Li, Guowei Deng, Qiusheng Zheng, Jun Lu, Defang LI*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number112867
JournalEuropean Journal of Medicinal Chemistry
Volume209
DOIs
Publication statusPublished - 1 Jan 2021

Scopus Subject Areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

User-Defined Keywords

  • Hypoxic
  • Melanoma
  • Photodynamic therapy
  • Porphycene
  • Tumor

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