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Cell Uptake of Steroid-BODIPY Conjugates and Their Internalization Mechanisms
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Resumo(s)
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.
Descrição
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.
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© 2023 by the authors.
Palavras-chave
androgen-BODIPY conjugates estradiol-BODIPY conjugates fluorescence imaging photodynamic therapy photosensitizers receptor-mediated cell uptake Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being