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类固醇-硼二吡咯缀合物的细胞摄取及其内化机制:癌症诊疗染料

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

作者信息

Amendoeira Ana F, Luz André, Valente Ruben, Roma-Rodrigues Catarina, Ali Hasrat, van Lier Johan E, Marques Fernanda, Baptista Pedro V, Fernandes Alexandra R

机构信息

Associate Laboratory i4HB, Institute for Health and Bioeconomy, NOVA School of Science and Technology, 2819-516 Caparica, Portugal.

UCIBIO-Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, 2819-516 Caparica, Portugal.

出版信息

Int J Mol Sci. 2023 Feb 10;24(4):3600. doi: 10.3390/ijms24043600.

DOI:10.3390/ijms24043600
PMID:36835012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9963437/
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 and 7α-Me-19-nortestosterone-BODIPY 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 and and 7α-Me-19-nortestosterone-BODIPY induced cell death, suggesting their potential for use as PDT agents.

摘要

通过8碳间隔链连接的雌二醇 - BODIPY以及通过乙炔基间隔基团连接的19 - 去甲睾酮 - BODIPY和睾酮 - BODIPY,利用荧光显微镜在乳腺癌细胞系MCF - 7和MDA - MB - 231、前列腺癌细胞系PC - 3和LNCaP以及正常皮肤成纤维细胞中进行了细胞摄取评估。观察到11β - OMe - 雌二醇 - BODIPY和7α - Me - 19 - 去甲睾酮 - BODIPY对表达其特异性受体的细胞具有最高水平的内化作用。阻断实验显示了癌症细胞和正常细胞中非特异性细胞摄取的变化,这可能反映了缀合物亲脂性的差异。缀合物的内化被证明是一个能量依赖过程,可能由网格蛋白和小窝介导的内吞作用介导。使用癌细胞和正常成纤维细胞的二维共培养研究表明,缀合物对癌细胞更具选择性。细胞活力测定表明,缀合物对癌细胞和/或正常细胞无毒。用雌二醇 - BODIPYs以及7α - Me - 19 - 去甲睾酮 - BODIPY孵育的细胞进行可见光照射会诱导细胞死亡,表明它们有作为光动力治疗剂的潜力。

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