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A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2021 Jan 01; Vol. 209, pp. 112867. Date of Electronic Publication: 2020 Sep 24. - Publication Year :
- 2021
-
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 LD <subscript>50</subscript> 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.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Crystallography, X-Ray
Humans
Light
Male
Melanoma metabolism
Melanoma pathology
Mice
Mice, Inbred BALB C
Models, Molecular
Photochemotherapy
Photosensitizing Agents chemistry
Porphyrins chemistry
Sulfonamides chemistry
Melanoma drug therapy
Photosensitizing Agents therapeutic use
Porphyrins therapeutic use
Sulfonamides therapeutic use
Tumor Hypoxia drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 209
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33010634
- Full Text :
- https://doi.org/10.1016/j.ejmech.2020.112867