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Bio-orthogonal catalysis for cancer therapy

Periodic Reporting for period 2 - THERACAT (Bio-orthogonal catalysis for cancer therapy)

Reporting period: 2020-03-01 to 2022-08-31

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 tackled this challenge in all its steps: from the synthesis of the catalysts to the in vivo biological evaluation. Novel pairs of catalytically active pro-drugs and catalysts have been designed and tested in various biological models from cells to animals. This led to both a better fundamental understanding of bio-orthogonal catalysis and to screen for the best performing material. The action is therefore successfully concluded and paved the way towards the development of novel catalytic materials with potential for cancer therapy, enhancing the career perspectives of the researchers recruited and providing 13 highly trained researchers prepared to tackle scientific relevant challenges in different sectors.
The THERACAT Network was fully established after the gender-balanced recruitment of 13 Early Stage Researchers (54% women – 46% men) and the formation of management structures and boards. A THERACAT webpage was launched that has been continuously updated all along the project (https://theracat.eu/) and a Twitter account was also launched (@theracatEU). Network Meetings have been conducted once a year and attended by ESRs and supervisors, with some extra meetings such the Midterm check Meeting with the Project Officer and a meeting for the ESRs to address COVID-19 pandemic related issues and promote collaboration.

At the training level, five 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); (4) Going in vivo, chemistry and cancer biology (M30); (5) Getting ready for the next career step (M36). All ESRs prepared their Personal Career Development Plans which have been updated yearly, finishing with a Personal Employment Plan. Moreover, assessment of ESRs has been performed every 6 months by the corresponding Assessment Commissions formed by supervisors from the Network having different profiles (academia/industry). Few secondments were also implemented but, unfortunately, they had to be finished earlier than planned due to COVID-19 outbreak. Alternative virtual activities were offered to the ESRs.

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 started 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 under implementation on the nanoparticles developed in the different nodes. A key discovery made at EDI has led to a patent in which an ESR is co-inventor.

At the dissemination level, ESRs have been actively involved presenting these results in international conferences, seminars and workshops, publishing peer-reviewed scientific articles, and participating in the THERACAT Final Conference. Moreover, results of the Network and its scientific approach have been also communicated to the general public through a video made by the ESRs, general press articles and participation of the ESRs in outreach activities of their institutions.
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.
THERACAT Network Consortium
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