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Bio-orthogonal catalysis for cancer therapy

Periodic Reporting for period 1 - THERACAT (Bio-orthogonal catalysis for cancer therapy)

Reporting period: 2018-03-01 to 2020-02-29

The global objective of the THERACAT Network is to train a new generation of researchers on the innovative topic of bio-orthogonal catalysis for cancer therapy. With the aim of establishing new and effective approaches for cancer therapies, catalytic nano- and microparticles are used. The proposed therapy consists of two steps. First these devices can be delivered or implanted in the tumour site. Second a pro-drug, that is an inactivated medicine, is given to the patient, this can circulate freely without performing any action. The nanodevices will convert this inactive compound into a potent drug able to kill the cell (catalysis). The power of this approach is that the nanoparticles will generate a high number of drugs only locally, resulting in an effective cancer therapy without the classical side effects of chemotherapy. The THERACAT consortium will tackle this challenge in all its steps: from the synthesis of the catalysts to the in vivo biological evaluation.
During the first 24 months of the project, the THERACAT Network has been fully established. Management structures and boards have been set, and a gender-balanced recruitment of 13 Early Stage Researchers has been achieved (54% women – 46% men). All ESRs except one are enrolled in a PhD Programme. The THERACAT webpage has been launched and is continuously updated (https://theracat.eu/). Three Network Meetings (Kick off, Month 12, Month 24) and the Midterm check Meeting with the Project Officer have been organized and attended by all ESRs and supervisors.

At the training level, three Training Events have been organized, including lectures from supervisors as well as from external invited experts: (1) How to plan and start a PhD (M12); (2) Chemical synthesis and catalysis (M18); (3) Drug delivery and microscopy (M24). All ESRs prepared their Personal Career Development Plan which is being updated yearly. Moreover, assessment of ESRs is performed every 6 months by the corresponding Assessment Commissions formed by supervisors from the Network having different profiles (academia/industry). The first secondments have also been implemented but, unfortunately, they have been finished earlier than planned due to COVID-19 outbreak.

At the scientific level, the initial work performed allowed to obtain key tools necessary that are now available or almost complete, including: microscopy methods (IBEC-TUE), pro-dyes and pro-drugs (TUE, EDI), catalysts (BAS, GRO, TEVA), catalytic nanoparticles (TAU, TUE) and in vitro (BGX) and in vivo (TAG, TAU) methods. In the last period the combination of such elements starts to give relevant results for the consortium. The imaging techniques developed have been applied to the study of the synthesized nanoparticles providing information about their behavior in vitro and in cells. Moreover, the catalysts screening led to the first hits and the selected catalysts are now under implementation on the nanoparticles developed in the different nodes. ESRs have presented these results in international conferences and seminars/workshops, being also actively involved in communication and outreach activities open to students at different levels and to the general public.
Two main points of impact are envisioned. First, new fundamental knowledge about the design and performances of synthetic catalysts in the biological environment will be provided. This will advance the whole field of bio-orthogonal catalysis. Second, we envision the realization of new devices for cancer therapy, with potential commercial and societal impact in the field of oncology.