We create DYNAFLUORS using a multidisciplinary approach that involves organic and peptide chemistry, fluorescence spectroscopy, cell biology and optical imaging. DYNAFLUORS are excellent imaging probes because they emit a fluorescent signal only after they interact with their target molecules (e.g. proteins, enzymes) or in specific microenvironments (e.g. organelles, high/low pH). With this approach, we obtain high signal-to-noise ratios and increased sensitivity, which allow DYNAFLUORS to be used in small doses, reducing any potential adverse effects and facilitating the translation to the clinic.
Smart probes for imaging macrophage activity.
Adapted from Chem. Soc. Rev., 2016, 45, 1182-1196. Published by the Royal Society of Chemistry
The innate immune system is our first line of defence against pathogen infection. We have developed DYNAFLUORS to image specific events different immune cells, either in the context of inflammatory diseases, cancer or metastasis. Our group is focused on creating imaging probes to analyse the roles that immune cells play in the tumour microenvironment. We have developed PhagoGreen as the first BODIPY-based small molecule to image phagocytic macrophages in vivo (JACS, 2013) and SOD Orange as the first small molecule to detect Cu/Zn superoxide dismutase in vivo (Chem. Commun., 2016). We have also adapted these technologies into theranostic probes (ACS Cent. Sci., 2017) with fluorophore-prodrug conjugates to target defined subpopulations of macrophages in vivo. We have invented triazole-based near-infrared photostable CIR dyes (Chem. Sci., 2018) for imaging T cells in vivo, SCOTfluors (Angew. Chem., 2019) for imaging metabolites and fluorescent activatable chemokines (Angew. Chem., 2019) as the first probes for imaging metastasis-associated macrophages. We have also recently developed Apo-15 as an imaging probe for imaging apoptotic cells in vitro and in vivo (Nat. Commun., 2020 and commercialised by BioLegend since 2019).
Representative fluorescent scaffolds covering the entire UV-Vis spectrum.
Reprinted with permission from Chem. Rev., 2012, 112, 4391–4420. Copyright 2012 American Chemical Society.
Innovative chemistry to prepare fluorogenic labels is fundamental in the development of better fluorescent probes. Our group has pioneered the adaptation of multicomponent reaction chemistry to prepare fluorophores with unprecedented chemical diversity (Angew. Chem., 2017). We have recently integrated this chemistry to prepare fluorogenic peptides in a minimally-invasive manner using a Trp-BODIPY amino acid (Nat. Commun., 2016, commercialised by Sigma-Merck since 2017). These methodologies will improve the way we prepare fluorescent imaging probes with high sensitivity and specificity (Nat. Protocols, 2017). Recent analogues include the optically-enhanced Trp(redBODIPY) for constructing red fluorogenic peptides (Chem. Sci. 2020). For a review on fluorescent amino acids for chemical biology and optical imaging, see Nat. Rev. Chem. 2020.