Prakasham A.P.

Project title: Enzyme mimics for in-vivo prodrug activation

Host Institution: Eindhoven University of Technology (TU/e)

Host Supervisor: Prof. Dr. Ir. Anja R.A. Palmans

Co-host Institution: École Polytechnique Fédérale de Lausanne (EPFL)

Co-host Supervisor: Prof. Dr. Harm-Anton Klok

Summary project: Cancer accounted in 2020 alone for close to 10 million deaths worldwide. Although intense research and advanced medical treatments dramatically improved a patient’s life expectancy and quality, treatments such as chemotherapy still cause severe side effects. Cancer cells are similar to normal cells, which makes it difficult to differentiate between them in treatments using anticancer drugs. The development of safe and selective chemotherapeutic drugs is therefore pivotal for reducing side effects in and enhancing the efficacy of cancer treatments. The bio-orthogonal catalytic approach aims to demask a caged (nontoxic) anticancer drug selectively at the cancer site by using an enzyme-like metal-based catalyst capable of performing a highly selective reaction that does not otherwise occur. The prodrug is then locally activated at the tumor site, and will only there induce cell apoptosis. Carefully engineered single-chain polymeric nanoparticles (SCPNs) are selected as the carrier material to guide the metal complex to the site of interest. SCPNs encapsulate and fold around the active metal-catalyst, and form nanometer-sized particles with a hydrophobic interior of defined size and shape. By attaching suitable targeting units to the hydrophilic corona, they can be safely delivered to target sites amidst complex cellular media. High catalytic activity and stability will give the SCPNs enzyme-like features. This project deals with the synthesis of active organometallic enzyme mimics, stabilized with N-heterocyclic carbene ligands, the use of SCPNs as carriers, and their demasking reactions for prodrug activation in complex cellular media.

Prakasham A.P.
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EuroTechPostdoc2 Programme

Within the EuroTechPostdoc2 programme, the universities of the EuroTech Universities Alliance offer seventy Marie Skłodowska-Curie fellowships to experienced high-potential researchers, in two calls for 35 fellows each. Besides giving the fellows the freedom to establish their own research lines, the programme provides exceptional training opportunities to prepare the fellows for a future as part of the new generation of scientific leaders, within and outside of academia.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 899987.

Supported by Eindhoven University of Technology. Designed by Penrose CDB – www.penrose-cdb.com