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肿瘤球体中的细胞活力成像 钌(II)光开关配合物的DNA结合

Cell viability imaging in tumor spheroids DNA binding of a ruthenium(II) light-switch complex.

作者信息

Ramu Vadde, Wijaya Lukas S, Beztsinna Nataliia, Van de Griend Corjan, van de Water Bob, Bonnet Sylvestre, Le Dévédec Sylvia E

机构信息

Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.

Leiden Academic Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.

出版信息

Chem Commun (Camb). 2024 Jun 13;60(49):6308-6311. doi: 10.1039/d4cc01425a.

Abstract

The famous ''light-switch'' ruthenium complex Ru(bpy)(dppz) (1) has been long known for its DNA binding properties . However, the biological utility of this compound has been hampered by its poor cellular uptake in living cells. Here we report a bioimaging application of 1 as cell viability probe in both 2D cells monolayer and 3D multi-cellular tumor spheroids of various human cancer cell lines (U87, HepG2, A549). When compared to propidium iodide, a routinely used cell viability probe, 1 was found to enhance the staining of dead cells in particular in tumor spheroids. 1 has high photostability, longer Stokes shift, and displays lower cytotoxicity compared to propidium iodide, which is a known carcinogenic. Finally, 1 was also found to displace the classical DNA binding dye Hoechst in dead cells, which makes it a promising dye for time-dependent imaging of dead cells in cell cultures, including multi-cellular tumor spheroids.

摘要

著名的“光开关”钌配合物Ru(bpy)(dppz)(1)因其与DNA的结合特性而早已为人所知。然而,该化合物的生物学效用因其在活细胞中的低细胞摄取率而受到阻碍。在此,我们报告了1作为细胞活力探针在各种人类癌细胞系(U87、HepG2、A549)的二维细胞单层和三维多细胞肿瘤球体中的生物成像应用。与常用的细胞活力探针碘化丙啶相比,发现1能增强死细胞的染色,尤其是在肿瘤球体中。1具有高光稳定性、更长的斯托克斯位移,并且与已知具有致癌性的碘化丙啶相比,显示出更低的细胞毒性。最后,还发现1能在死细胞中取代经典的DNA结合染料Hoechst,这使其成为用于细胞培养(包括多细胞肿瘤球体)中死细胞的时间依赖性成像的一种有前景的染料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c1/11181008/f38acdb3c88b/d4cc01425a-s1.jpg

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