Pinkment: a synthetic platform for the development of fluorescent probes for diagnostic and theranostic applications |
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Authors: | Maria Weber,Hai-Hao Han,Bo-Han Li,Maria L. Odyniec,Charlotte E. F. Jarman,Yi Zang,Steven D. Bull,Amanda B. Mackenzie,Adam C. Sedgwick,Jia Li,Xiao-Peng He,Tony D. James |
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Abstract: | Reaction-based fluorescent-probes have proven successful for the visualisation of biological species in various cellular processes. Unfortunately, in order to tailor the design of a fluorescent probe to a specific application (i.e. organelle targeting, material and theranostic applications) often requires extensive synthetic efforts and the synthetic screening of a range of fluorophores to match the required synthetic needs. In this work, we have identified Pinkment-OH as a unique “plug-and-play” synthetic platform that can be used to develop a range of ONOO− responsive fluorescent probes for a variety of applications. These include theranostic-based applications and potential material-based/bioconjugation applications. The as prepared probes displayed an excellent sensitivity and selectivity for ONOO− over other ROS. In vitro studies using HeLa cells and RAW 264.7 macrophages demonstrated their ability to detect exogenously and endogenously produced ONOO−. Evaluation in an LPS-induced inflammation mouse model illustrated the ability to monitor ONOO− production in acute inflammation. Lastly, theranostic-based probes enabled the simultaneous evaluation of indomethacin-based therapeutic effects combined with the visualisation of an inflammation biomarker in RAW 264.7 cells. Pinkment, a resorufin based ONOO− selective and sensitive ‘plug and play’ fluorescence-based platform for in vitro and in vivo use, enables facile functionalisation for various imaging and theranostic applications. |
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