Cell Uptake of Steroid-BODIPY Conjugates and Their Internalization Mechanisms: Cancer Theranostic Dyes

Abstract

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.

BODIPY-Based Molecules for Biomedical Applications

“…Considerable efforts have been made to create successful cancer therapies, such as surgery, chemotherapy, radiation therapy, immunotherapy, photodynamic therapy, photothermal gered by light [25]. These substances can be coupled with molecules that target cancer cells to increase their selectivity towards those cells while minimizing damage to healthy tissues [26,27]. Additionally, BODIPY dyes can be engineered to emit fluorescence, allowing for real-time monitoring of their distribution and therapeutic effects [28].…”

A Study on the Structure, Optical Properties and Cellular Localization of Novel 1,3-Benzothiazole-Substituted BODIPYs

“…BODIPY dyes tend to aggregate in aqueous solutions and have a tendency to concentrate in lipophilic compartments in cells, which may result in non-specific staining of cell membranes and other organelles [29,30]. Hence, to increase hydrophilicity and reduce non-specific fluorescence, the BODIPY scaffold has been decorated with a variety of polar groups [31][32][33].…”