Selective fluorescent probes for molecular imaging of ROS/RNS: Challenges and opportunities

Abstract

An ever expanding array of biological processes such as development, aging, inflammation, immunity, cancer and neurodegeneration is dynamically sculpted by chemical mediators – reactive oxygen/nitrogen species (ROS/RNS) including superoxide anion radical (O2•–), hydrogen peroxide (H2O2), hydroxyl radical (•OH), hypochlorous acid (HOCl) and peroxynitrite (ONOO–). The formation, metabolism and detoxification of ROS/RNS contribute to human health and disease in complex ways, while heterogeneity in chemical behavior of ROS/RNS in cells renders selective detection of single ROS/RNS extremely challenging. With their intrinsic advantages such as high sensitivity, practical handling, inexpensive instrumentation, and ease of functional modifications, small-molecule fluorescent probes represent an ideal biorthogonal approach to ROS/RNS detection. Here we report novel sensing strategies and development of the HKGreen, 1-4 HKSOX, 5 HKOCl, 6,7 and HKOH series of fluorescent probes for the detection and molecular imaging of ONOO–, O2•–, HOCl, and •OH, respectively, featuring excellent selectivity and sensitivity toward the target species. In several platforms including live cell confocal imaging, microplate assay, flow cytometry, tissue staining and in vivo zebrafish imaging, the applicability of the probes has been thoroughly validated. Overall, these probes offer exciting opportunities for selective detection and molecular imaging of single ROS/RNS with greater depth, resolution and confidence.

Acknowledgements: This work was supported the by The University of Hong Kong, the University Development Fund, Hong Kong Research Grants Council (HKU 706410, HKU 706410P and HKU 17305714), and Morningside Foundation.

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