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

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...

Full description

Saved in:
Bibliographic Details
Published in:European journal of medicinal chemistry 2021-01, Vol.209, p.112867-112867, Article 112867
Main Authors: Wang, Yuzhi, Pan, Zhaohai, Cheng, Xiao-Lan, Zhang, Kai, Zhang, Xin, Qin, Yao, Fan, Jiaojiao, Yan, Ting, Han, Tao, Shiu, Kwok Keung, Hau, Sam Chun-Kit, Mak, Nai-Ki, Kwong, Daniel W.J., Liu, Xiaona, Li, Minjing, Deng, Guowei, Zheng, Qiusheng, Lu, Jun, Li, Defang
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Crystallography, X-Ray
Humans
Hypoxic
Light
Male
Melanoma
Melanoma - drug therapy
Melanoma - metabolism
Melanoma - pathology
Mice
Mice, Inbred BALB C
Models, Molecular
Photochemotherapy
Photodynamic therapy
Photosensitizing Agents - chemistry
Photosensitizing Agents - therapeutic use
Porphycene
Porphyrins - chemistry
Porphyrins - therapeutic use
Sulfonamides - chemistry
Sulfonamides - therapeutic use
Tumor
Tumor Hypoxia - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. [Display omitted] •Two novel porphycene-based photosensitizers were designed and synthesized.•TBPoS-OH and TBPoS-2OH possess photo-cytotoxicity with a LD50 in the nM range.•TBPoS-OH mainly localized lysosomes and subsequently induced cell apoptosis.•TBPoS-OH significantly reduced tumor growth in two xenografted mouse models.•TBPoS-OH exhibited no obvious immunogenicity and toxicity in mice.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2020.112867