Fluorescent Probes in Drug Discovery and Precision Medicine

Abstract:

Activatable fluorogenic probes that remain weakly emissive until they encounter a defined biomolecular environment provide high-contrast readouts in living systems. Our work has focused on translating this principle into a wide range of chemical structures, from fluorescent amino acids

[1] to peptides[2] and proteins[3]. The central design criteria are that these probes should be synthetically accessible while minimally perturbing the recognition features of the parent biomolecule, and switch on preferentially upon productive target engagement, thereby enabling wash-free imaging and improved signal-to-noise ratios in complex samples.[4]Using this platform, we have developed fluorogenic probes for infection, inflammation and immunology that operate in live cells, human biosamples, in vivo models and fresh ex vivo biopsies. Recent advances include fluorescent amino acids for peptide-PAINT and super-resolution microscopy, which reduce linkage error while retaining strong environmental sensitivity,[5] and fluorogenic tags for functionally important immune proteins such as interleukins and chemokines.[6] The same molecular design principles have also been extended to nanobodies and antibodies, generating targeted imaging agents that preserve high affinity and biological function.[7]

Current efforts focus on controlling excited-state behaviour and activation pathways for therapeutic labelling and targeted imaging. By tuning fluorophore electronics, conformational freedom and microenvironment sensitivity, we have generated minimally perturbing labels that report internalisation and trafficking of antibody-drug conjugates in drug-discovery studies with pharmaceutical partners.[8] In parallel, we are extending beyond intensity-based outputs through biocompatible thermally activated delayed fluorescence (TADF) probes for highly multiplexed fluorescence lifetime imaging[9] and activity-based chemiluminescent reagents.[10] These complementary chemical platforms broaden the toolbox for cell-targeted imaging agents and precision-medicine studies in patient-derived samples with clinical collaborators.

[1] a) Mendive-Tapia, L. et al. Nat. Commun. 2016, 7, 10940. b) Mendive-Tapia, L. et al. Angew. Chem. Int. Ed. 2022, 61, e202117218.
[2] a) Barth, N. et al. Nat. Commun. 2020, 11, 4027. b) Scott, J. et al. Nat. Commun. 2022, 13, 2366.
[3] a) Reese, A. et al. ACS Cent. Sci. 2024, 10, 143. b) Harel et al. J. Am. Chem. Soc. 2025, 147, 42647.
[4] For reviews, see: a) Cheng, Z. et al. Nat. Rev. Chem. 2020, 4, 275. b) Seah et al. ACS Nano 2023, 17, 19478. c) De Moliner, F. et al. Curr. Opin. Chem. Biol. 2024, 80, 102458.
[5] De Moliner, F. et al. Angew. Chem. Int. Ed. 2023, 62, e202216231.
[6] a) Bertolini, M. et al. J. Am. Chem. Soc. 2025, 147, 47783. b) Reese, A. et al. Chem. Sci. 2026, doi: 10.1039/D5SC09634K
[7] a) Kuru, E. et al. Nat. Commun. 2024, 15, 7531. b) Bertolini, M. et al. J. Am. Chem. Soc. 2024, 46, 30565.
[8] Nadal-Bufi, N. et al. J. Am. Chem. Soc. 2025, 147, 7578.
[9] Suarez de Cepeda et al. Angew. Chem. Int. Ed. 2026, e21482.
[10] Scott et al. Nat. Biomed. Eng. 2026, doi: 10.1038/s41551-025-01588-1.

Short bio:

Prof Marc Vendrell began his independent career at the University of Edinburgh in 2012 as an Academic Fellow to bridge Chemistry and Medicine through the development and translation of chemical probes for biomedical imaging and drug discovery. Since 2020, he holds a Personal Chair of Translational Chemistry and Biomedical Imaging and leads the IRR Chemistry Hub at the College of Medicine and Veterinary Medicine, one of the first hubs for collaborative “Chemistry in Medicine” research. His group has pioneered activatable fluorophores, fluorogenic amino acids and optical imaging probes with applications in high-resolution biological imaging, immune-cell tracking, clinical diagnostics and translational medicine. Their discoveries have led to 10 licensed and commercialised research-use-only technologies, and some observational clinical studies in several hospitals across Europe. He is co-inventor of 15 patents and has established major collaborations with clinical teams, biotech companies and global pharmaceutical partners in Europe, USA and Asia. Prof Vendrell has received >£12M funding as PI -with several ERC and EIC grants- and numerous distinctions, including Fellow of the Royal Society of Chemistry (2017), Marcial Moreno Lectureship (2018), FLIER Fellow from the Academy of Medical Sciences (2019), SRUK Emerging Talent Award (2019), Bader Prize from the Royal Society of Chemistry (2023), Daiwa Foundation Award (2025) and the Research Excellence Award from the Spanish Royal Society of Chemistry (2026). In 2024, he was elected Fellow of the Royal Society of Edinburgh, the Scottish national academy.

This seminar is hosted by Javier Urieta 

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