The objective of the THERACAT network is to train through research a new generation of researchers in bio-orthogonal catalysis for cancer therapy.
THERACAT proposes new solutions for more effective and side effect-free chemotherapy. The key feature of THERACAT strategy is the use of bio-orthogonal catalysis to activate chemotherapeutic prodrugs selectively and efficiently in the tumor site. The development of a chemical arsenal of catalysts able to function in the complex biological media is therefore a main scientific target of the project.
In order to exploit the therapeutic potential of bio-orthogonal catalysis, several scientific and technical issues have to be addressed such as: i) the availability of metal-labile protective groups fully stable under physiological conditions; ii) highly stable and active catalysts system that can be implanted or targeted at the site of interest; and iii) a full understanding of in vivo catalysts localization, catalytic activity, toxicity and anticancer activity. Clearly these challenges exceed the field of chemistry and catalysis and require a broad expertise in a variety of fields ranging from chemistry and catalysis to biology and imaging. The THERACAT consortium comprises several renowned European players, both academic and industrial, in fields necessary for the development of bio-orthogonal therapies and combines the knowledge required starting from material synthesis, catalysis activation, in vitro and in vivo cancer cell studies up to in vivo animal studies to test the efficacy of the developed systems.
The research programme of the Network is organized into 4 research Work Packages (WPs):
WP3 – Catalysts synthesis. In WP3, THERACAT will evaluate a number of transition-metal-based catalysts with the ultimate aim to activate selected, clinically relevant chemotherapeutic agents that are currently applied in cancer treatment therapies.
WP4 – Prodrugs design and synthesis. The aims of WP4 are to expand the arsenal of therapeutics that can be activated by bio-orthogonal organometallic catalysts and to develop novel spectroscopy and microscopy methods that will enable to test the probe/prodrug activating capacity of the nanomaterials proposed in THERACAT by measuring single fluorescent events.
WP5 – In vitro delivery and imaging. The pairs of catalytic materials and prodrugs developed in WP3 and WP4 will be evaluated in in vitro biological models.
WP6 – In vivo evaluation. Main purpose of WP6 is to establish mCherry-labeled orthotopic models of cancer in mice. Then, we will evaluate the biodistribution of the newly synthesized prodyes and catalysts and the anticancer activity of the activated prodrugs in vivo.