Optical imaging has revolutionised our understanding of how biological systems behave at a molecular level. In our group we develop Dynamic Activatable Fluorophores (DYNAFLUORS) as chemical probes to image molecular events associated to infection, inflammation and cancer. With DYNAFLUORS, we aim to interrogate fundamental biology in real time as well as provide better tools to diagnose and treat disease in 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 health and disease. 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. We have invented triazole-based near-infrared photostable CIR dyes (Chem. Sci., 2018) for imaging T cells in vivo, SCOTfluors (Angew. Chem., 2019a and commercialised by Tocris) and Raman tags (Angew. Chem., 2021b) for imaging metabolites and fluorescent activatable chemokines (Angew. Chem., 2019b) as the first probes for imaging metastasis-associated macrophages.
We have also recently developed Apotracker Green (Apo-15) as an imaging probe for imaging apoptotic cells in vitro and in vivo (Nat. Commun., 2020 and commercialised by BioLegend) and Apotracker Red (Angew. Chem., 2022) We have also constructed chemiluminescent probes for imaging NK cell function in tumours in vivo (Angew. Chem., 2021a) and T cell function in drug screens (Nat. Commun., 2021b).
SMALL FLUOROGENIC LABELS
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 MilliporeSigma). 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). We have recently reviewed the advances in fluorescent amino acids for chemical biology (Nat. Rev. Chem., 2020). Using this chemistry, we have also developed the smallest photosensitizers reported to date and their use and photoactivatable metabolites for photodynamic therapy in vivo (Nat. Commun., 2021a).
TRANSLATION, TRANSLATION, TRANSLATION
One of our main objectives (and motivations!) is to deliver high-impact translational research by working with clinicians to bring new imaging probes to clinical trials and with industry to commercialise new technologies.