RT Journal Article
T1 BASHY Dyes Are Highly Efficient Lipid Droplet-Targeting Photosensitizers that Induce Ferroptosis through Lipid Peroxidation
A1 Santos Alves Silva, Maria José dos
A1 Fernández Arteaga, Jesús
A1 Pischel, Uwe
A1 Gois, Pedro
AB 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; ΦΔ 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 IC50 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)
PB American Chemical Society
SN 1043-1802
SN 1520-4812 (electrónico)
YR 2023
FD 2023-11
LK https://hdl.handle.net/10272/24356
UL https://hdl.handle.net/10272/24356
LA eng
NO Silva, M. J. S. A., Zhang, Y., Vinck, R., Santos, F. M. F., António, J. P. M., Gourdon-Grünewaldt, L., Zaouter, C., Castonguay, A., Patten, S. A., Cariou, K., Boscá, F., Nájera, F., Arteaga, J. F., Gasser, G., Pischel, U., & Gois, P. M. P. (2023). BASHY Dyes Are Highly Efficient Lipid Droplet-Targeting Photosensitizers that Induce Ferroptosis through Lipid Peroxidation. In Bioconjugate Chemistry (Vol. 34, Issue 12, pp. 2337–2344). American Chemical Society (ACS). https://doi.org/10.1021/acs.bioconjchem.3c00449
NO The authors acknowledge the financial support from Fundação para a Ciência e a Tecnologia, Ministério da Ciência e da Tecnologia, Portugal (SFRH/BD/132710/2017 to M.J.S.A.S., 2021.04125.CEECIND to F.M.F.S., 2022.06817.CEECIND to J.P.M.A.). The Research Institute for Medicines (iMed.ULisboa) acknowledges the financial support of Fundação para a Ciência e Tecnologia (projects PTDC/QUI-OUT/3989/2021; UIDB/04138/2020 and UIDP/04138/2020). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project N° 022161 (cofinanced by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). We thank the Spanish Ministry of Science and Innovation (PID2020-119992GB-I00 for U.P.; PID2019-104293GB-I00 for F.N.; PID2019-110441RB-C33 for F.B.), the Valencian Agency for Innovation (I-NNEST/2021/75 for F.B.), and the University of Huelva/Junta de Andalucía (UHU202070 for U.P.) for support. Furthermore, we are indebted to the Supercomputing and Bioinformatics Centre (SCBI) of the University of Malaga for providing the computer resources used for the theoretical calculations. Y.Z. thanks the China Scholarship Council for funding. This work was also financially supported by an ERC Consolidator Grant PhotoMedMet to G.G. (GA 681679) and by Qlife prématuration funding (G.G. and R.V.) and has received support under the program “Investissements d’Avenir” launched by the French Government and implemented by the ANR with the reference ANR-10-IDEX-0001-02 PSL (G.G.). L.G.-G. thanks the ENS-PSL for her PhD fellowship. We thank Francisco Germán Blandón (Univ. Huelva) for technical support. L.G.-G. thanks the École Normale Supérieure – PSL for her PhD fellowship. This study was supported by the Fond de Recherche du Québec - Nature et Technologies (FRQNT - Samuel-de-Champlain; L.G.-G., K.C., A.C., G.G., and S.A.P.), the Canada Foundation for Innovation (CFI; S.P. and A.C.), and the Natural Sciences and Engineering Research Council of Canada (NSERC; S.P. and A.C.). S.P. holds a Fond de Recherche du Québec - Santé (FRQS) Junior 2 research scholar award and the Anna Sforza Djoukhadjian Research Chair. We thank Pierre Burckel for help on ICP-MS.
DS Repositorio Institucional de la Universidad de Huelva
RD 30 may 2026