H2020Individual fellowship2017–2018

FLUORODRUGS · Smart Theranostic Agents for the Tumour Microenvironment

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-01-01 → 2018-12-31
EU contribution
€195,455
Participants
1
Scheme
MSCA-IF-EF-ST

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Results in brief

Smart Theranostic Agents for the Tumour Microenvironment

The main aim of FLUORODRUGS was to design, synthesise and validate novel smart chemical agents for highly sensitive and specific treatment of cancer and inflammation. During the course of this project I have developed new chemical strategies to prepare activatable fluorescent probes as real-time imaging tools for immune cells. Notably, the visualization of immune cells in the tumour microenvironment has allowed monitoring cancer progression in real time and discovering new biomarkers for cancer targeting. Furthermore, I have prepared novel theranostic agents with the ability of visualise in real-time as well as modulate specific macrophage subpopulations in vivo. This is a unique platform to generate highly specific tools allowing personalised treatment and real-time monitoring of cancer progression. (Figure 1)

Data: CORDIS, © European Union

Project objective

FLUORODRUGS is a highly interdisciplinary project encompassing the design, synthesis and biological validation of novel smart chemical agents for highly sensitive diagnosis and specific treatment of cancer. I will prepare novel drug-fluorophores conjugates by combining macrophage-specific fluorophores with cytotoxic drugs using smart cleavable linkers. The activation of these smart agents in the tumour microenvironment will allow to not only to visualise in real-time but also to selectively ablate tumour-associated macrophages, which are essential for cancer progression. Further derivatization of the agents with specific ligands (i.e. chemokine CCL2) will yield probes for specific subpopulations of macrophages (i.e. CCR2+ macrophages) that are critical in tumour metastasis. This strategy will minimise two of the major limitations of conventional cancer therapies: 1) drug resistance from cancer cells, and 2) toxic side effects derived from low cell specificity. Notably, the visualisation of immune cells in the tumour microenvironment will allow to monitor cancer progression in real-time and to run profiling studies to discover new biomarkers for cancer therapy. Initial in vitro studies to confirm the activity and selectivity of FLUORODRUGS will be performed in bone marrow-derived macrophages. Further, relevant mouse cancer models will be used to validate the theranostic agents in vivo. FLUORODRUGS will involve multidisciplinary training in biology, spectroscopy, pharmacology and imaging, and will render a unique generation of smart chemical tools to enhance diagnosis and treatment of cancer. This project will open a whole range of opportunities for my future career development in cancer biology and medicinal chemistry.

Original text from CORDIS.

Participants

Links

Data: CORDIS, © European Union