TY - JOUR
T1 - Cell Uptake of Steroid-BODIPY Conjugates and Their Internalization Mechanisms
T2 - Cancer Theranostic Dyes
AU - Amendoeira, Ana F.
AU - Luz, André
AU - Valente, Ruben
AU - Roma-Rodrigues, Catarina
AU - Ali, Hasrat
AU - van Lier, Johan E.
AU - Marques, Fernanda
AU - Baptista, Pedro V.
AU - Fernandes, Alexandra R.
N1 - info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0140%2F2020/PT#
info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F124612%2F2016/PT#
Funding Information:
This work was financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., within the scope of the projects of the Ministry of Science Technology and Higher Education: the project of the Associate Laboratory Institute for Health and Bioeconomy—i4HB and, in part, by the Jeanne and J.-Louis Lévesque foundation, Montreal, QC, Canada (J.E.v.L.). J.E.v.L. is a member of the Research Center of the CHUS (CRCHUS), Sherbrooke, QC, Canada, supported by the Fonds de la Recherche du Québec—Santé. C.R.R., A.L. and R.V. were funded by FCT/MCTES, grant numbers SFRH/BD/12161/2022, and SFRH/BD/09845/2022, respectively.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/2/10
Y1 - 2023/2/10
N2 - Estradiol-BODIPY linked via an 8-carbon spacer chain and 19-nortestosterone- and testosterone-BODIPY linked via an ethynyl spacer group were evaluated for cell uptake in the breast cancer cell lines MCF-7 and MDA-MB-231 and prostate cancer cell lines PC-3 and LNCaP, as well as in normal dermal fibroblasts, using fluorescence microscopy. The highest level of internalization was observed with 11β-OMe-estradiol-BODIPY 2 and 7α-Me-19-nortestosterone-BODIPY 4 towards cells expressing their specific receptors. Blocking experiments showed changes in non-specific cell uptake in the cancer and normal cells, which likely reflect differences in the lipophilicity of the conjugates. The internalization of the conjugates was shown to be an energy-dependent process that is likely mediated by clathrin- and caveolae-endocytosis. Studies using 2D co-cultures of cancer cells and normal fibroblasts showed that the conjugates are more selective towards cancer cells. Cell viability assays showed that the conjugates are non-toxic for cancer and/or normal cells. Visible light irradiation of cells incubated with estradiol-BODIPYs 1 and 2 and 7α-Me-19-nortestosterone-BODIPY 4 induced cell death, suggesting their potential for use as PDT agents.
AB - Estradiol-BODIPY linked via an 8-carbon spacer chain and 19-nortestosterone- and testosterone-BODIPY linked via an ethynyl spacer group were evaluated for cell uptake in the breast cancer cell lines MCF-7 and MDA-MB-231 and prostate cancer cell lines PC-3 and LNCaP, as well as in normal dermal fibroblasts, using fluorescence microscopy. The highest level of internalization was observed with 11β-OMe-estradiol-BODIPY 2 and 7α-Me-19-nortestosterone-BODIPY 4 towards cells expressing their specific receptors. Blocking experiments showed changes in non-specific cell uptake in the cancer and normal cells, which likely reflect differences in the lipophilicity of the conjugates. The internalization of the conjugates was shown to be an energy-dependent process that is likely mediated by clathrin- and caveolae-endocytosis. Studies using 2D co-cultures of cancer cells and normal fibroblasts showed that the conjugates are more selective towards cancer cells. Cell viability assays showed that the conjugates are non-toxic for cancer and/or normal cells. Visible light irradiation of cells incubated with estradiol-BODIPYs 1 and 2 and 7α-Me-19-nortestosterone-BODIPY 4 induced cell death, suggesting their potential for use as PDT agents.
KW - androgen-BODIPY conjugates
KW - estradiol-BODIPY conjugates
KW - fluorescence imaging
KW - photodynamic therapy
KW - photosensitizers
KW - receptor-mediated cell uptake
UR - http://www.scopus.com/inward/record.url?scp=85149017122&partnerID=8YFLogxK
U2 - 10.3390/ijms24043600
DO - 10.3390/ijms24043600
M3 - Article
C2 - 36835012
AN - SCOPUS:85149017122
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 4
M1 - 3600
ER -
