MACROIMAGING · Specific Fluorogenic Peptides for Imaging Metastasis-associated Macrophages

Specific Fluorogenic Peptides for Imaging Metastasis-associated Macrophages

Cancer is one of the leading causes of death worldwide, accounting for more than 8 million deaths in 2012 and with predictions of over 20 million new cancer cases each year by 2030. Cancer is also one of the public health priorities for the EU2 as it is necessary to create effective patient-oriented therapies. The metastatic potential of tumours is defined by the tumour microenvironment (TM), where immune cells are the most abundant cells. There is a need for new imaging probes that can selectively report cellular events with high sensitivity and spatiotemporal resolution in real-time. MACROIMAGING is a highly interdisciplinary project encompassing the design, preparation and biological characterization of innovative fluorogenic tools by playing at the interface between peptides, immunology and real-time optical imaging. The two main scientific objectives are: 1. Immune cells (e.g. macrophages) are fundamental in the development of the tumour microenvironment and metastasis. However, the role of macrophages in the TM remains elusive mainly because of the lack of technologies to target these unique populations of cells in vivo. MACROIMAGING aimed at developing the first generation of chemical probes that enable us to visualize with high resolution and target with high selectivity subpopulations of immune cells, in order to maximize therapeutic effect and reduce side effects. The project has provided optical probes that can selectively light up inside specific subpopulations of macrophages and, if conjugated to drugs, also elicit a selective cytotoxic response. 2. Peptides are biopolymers with outstading target specificity and low biotoxicity, properties that have boosted its use as marketed drugs in the past decades. In example, there are several peptide sequences that have been identified as potential cancer biomarkers. However, there is a lack of suitable fluorescent labelling methods that allow for real-time imaging without hampering peptide affinity. MACROIMAGING delivers Trp-BODIPY as an exceptional fluorogenic amino acid with outstanding optical properties that can be incorporated into any peptide sequence with minimal impact on its binding properties. As proof of concept, Trp-BODIPY has been applied to report fungal infection in real-time and to selectively visualize apoptotic vesicles, which play a role in the formation of the pre-metastatic niche.

Data: CORDIS, © European Union