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Activatable Fluorescent Probes as Smart Diagnostic Tools for Microendoscopy Imaging

Final Report Summary - ENDOIMAGE (Activatable Fluorescent Probes as Smart Diagnostic Tools for Microendoscopy Imaging)

Impact and advancement in the field.

The main aim of ENDOIMAGE was the development of new chemical strategies to produce activatable fluorescent probes as real-time imaging tools. During the course of the project, Vendrell has developed probes targeting biomarkers in cancer, inflammation and infection, which are areas of high unmet clinical need. Vendrell has also made significant advances to overcome two of the main limitations of current fluorophores for live cell imaging. First, the limited methods to synthesize fluorophores. He has addressed that by expanding the range of chemical modifications in fluorescent scaffolds reporting the first examples of multicomponent reactions (JACS 2013, Angewandte Chemie 2017, ACS Central Science 2017) and Pd-catalysed C-H activation (Nature Communications 2016) in BODIPY dyes. Second, he has pioneered Trp-BODIPY as a new tool to prepare fluorescent peptides without impairing the molecular recognition properties (Nature Protocols 2017, Chemical Communications 2017). Trp-BODIPY is now commercialised worldwide, with remarkable impact in the whole scientific community, particularly in the field of chemical biology. These new methodologies developed by Vendrell have the potential to transform the way we monitor disease and therapy efficacy in humans, in combination with suitable clinical imaging modalities.

Project Objectives

The overarching goal of ENDOIMAGE was to develop activatable fluorescent probes as novel optical imaging for cancer and infection. The outcomes in the different subtopics are detailed below.
New chemistry. Vendrell has pioneered synthetic methodologies in fluorescent probe development that had been limited to areas like medicinal chemistry (e.g. multicomponent reactions and C-H activation). With these, he has generated probes improving the selectivity and sensitivity of current tools preclinical and translational imaging. This strategy has led to remarkable progress in the development of new chemical structures and methodologies for molecular optical imaging in medical areas of unmet need. The track-record during the project has been exceptional with 15 publications (14 of them as corresponding author) including high-impact publications in Nature Communications, Nature Protocols, JACS and Angewandte Chemie, and one international patent. Vendrell has been also invited to give over 25 lectures and seminars, locally, nationally and abroad.
Biological validation. Vendrell has drawn widely to collaborate within Edinburgh and beyond (including industry) to validate the utility of his chemical probes selectivity and specificity in relevant cell lines and tissues using cutting-edge biological imaging assays (e.g. multiphoton microscopy, intravital microscopy). These studies put him in a strong position to apply for translational funding to solve current research challenges in medicine and healthcare.
Collaborative network and international profile. As part of the reintegration to Europe, one key aspect of the project was to ensure his integration in the Host Institute as well as to establish a powerful network of collaborators nationally and internationally. Vendrell has established multiple collaborations with world-leaders in chemistry (Bradley, Liskamp, Chang, Schultz), cancer biology (Frame, Pollard) and fungal cell biology (Read), among others, allowing him to interrogate the utility of the probes in vivo in relevant multicellular models and ex vivo human tissue. Vendrell has built an international profile in the field of chemical imaging, with several high-impact publications in scientific journals and patents, presentations at international meetings, participation in academic activities and knowledge transfer with the industry. He is becoming one of the future young leaders in the field of chemical imaging.
Transfer of knowledge, including outreach activities. Vendrell has been actively involved in several activities for the transfer of knowledge to the Host Institution by lecturing several courses to undergraduate and postgraduate students in the School of Chemistry and the College of Medicine. Vendrell has been also actively involved in the organisation of outreach activities and since 2015 been appointed STEM Ambassador and member of the CIR Science Festivals Subcommittee, which participates in the organisation of activities (e.g. Edinburgh International Science Festival) to communicate science to the general public. A personal website has been created and is regularly updated (http://www.dynafluors.co.uk) to disseminate all the outcomes and scientific activities in Vendrell’s group.