Silva, Maria J S A; Zhang, Yiyi; Vinck, Robin; Santos, Fabio M.F.; António, Joao P. M.; Gourdon-Grünewaldt, Lisa; Zaouter, Charlotte; Castonguay, Annie 
ORCID: https://orcid.org/0000-0001-5705-6353; Patten, Shunmoogum A. ORCID: https://orcid.org/0000-0002-2782-3547; Cariou, Kevin; Boscá, Francisco; Nájera, Francisco; Arteaga, Jesus F.; Gasser, Gilles; Pischel, Uwe et Gois, Pedro M. P.
(2023).
BASHY Dyes Are Highly Efficient Lipid Droplet-Targeting Photosensitizers that Induce Ferroptosis through Lipid Peroxidation
Bioconjugate Chemistry
, vol. 34
, nº 12.
pp. 2337-2344.
DOI: 10.1021/acs.bioconjchem.3c00449.
Résumé
Ferroptosis is an iron-dependent lipid-peroxidation-driven mechanism of cell death and a promising therapeutic target to eradicate cancer cells. In this study, we discovered that boronic acid-derived salicylidenehydrazone (BASHY) dyes are highly efficient singlet-oxygen photosensitizers (PSs; Φ(Δ) up to 0.8) that induce ferroptosis triggered by photodynamic therapy. The best-performing BASHY dye displayed a high phototoxicity against the human glioblastoma multiform U87 cell line, with an IC(50) value in the low nanomolar range (4.40 nM) and a remarkable phototoxicity index (PI > 22,700). Importantly, BASHY dyes were shown to accumulate in lipid droplets (LDs) and this intracellular partition was found to be essential for the enhanced phototoxicity and the induction of ferroptosis through lipid peroxidation. The safety and phototoxicity of this platform were validated using an in vivo zebrafish model (Danio rerio).
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 04 janv. 2024 14:45 |
| Dernière modification: | 04 janv. 2024 14:45 |
| URI: | https://espace.inrs.ca/id/eprint/13945 |
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