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DOTAM-based, targeted, activatable fluorescent probes for the highly sensitive and selective detection of cancer cells

Item Type:Article
Title:DOTAM-based, targeted, activatable fluorescent probes for the highly sensitive and selective detection of cancer cells
Creators Name:Brennecke, B. and Wang, Q. and Haap, W. and Grether, U. and Hu, H.Y. and Nazaré, M.
Abstract:The utilization of an activatable, substrate-based probe design in combination with a cellular targeting approach has been rarely explored for cancer imaging on a small-molecule basis, although such probes could benefit from advantages of both concepts. Cysteine proteases like cathepsin S are known to be involved in fundamental processes associated with tumor development and progression and thus are valuable cancer markers. We report the development of a combined dual functional DOTAM-based, RGD-targeted internally quenched fluorescent probe that is activated by cathepsin S. The probe exhibits excellent in vitro activation kinetics which can be fully translated to human cancer cell lines. We demonstrate that the targeted, activatable probe is superior to its nontargeted analog, exhibiting improved uptake into α(ν)β(3)-integrin expressing human sarcoma cells (HT1080) and significantly higher resultant fluorescence staining. However, profound activation was also found in cancer cells with a lower integrin expression level, whereas in healthy cells almost no probe activation could be observed, highlighting the high selectivity of our probe toward cancer cells. These auspicious results show the outstanding potential of the dual functionality concept combining a substrate-based probe design with a targeting approach, which could form the basis for highly sensitive and selective in vivo imaging probes.
Keywords:Fluorescent Dyes, Neoplasms, Optical Imaging, Sensitivity and Specificity, Tumor Cell Line
Source:Bioconjugate Chemistry
Publisher:American Chemical Society
Page Range:702-712
Date:21 April 2021
Official Publication:https://doi.org/10.1021/acs.bioconjchem.0c00699
PubMed:View item in PubMed

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