Project description
Enzyme-triggered drug delivery for cancer
Delivering therapeutic molecules directly into cancer cells remains one of the most persistent challenges in oncology. While numerous peptide-based compounds exhibit considerable promise as anticancer agents, their clinical utility is often limited by rapid degradation in biological systems and insufficient cellular uptake. With the support of the Marie Skłodowska-Curie Actions programme, the TRACE project will work to develop smart drug delivery vehicles called biomolecular condensates that are designed to self-assemble from peptide building blocks and disassemble specifically in response to enzymes that are overactive in tumour cells. This is intended to precisely release cytotoxic peptidomimetics directly at the tumour site. Using fluorescent tags for real-time imaging, researchers will track condensate formation and drug release, validating the approach against key cancer-relevant molecular targets involved in cell division and survival.
Objective
Intracellular delivery of unmodified therapeutic peptides remains a major challenge in targeted cancer therapy, due to poor cell permeability and rapid degradation. This fellowship addresses that limitation by developing enzyme-triggered biomolecular condensates (BMCs) as a spatiotemporally controlled delivery platform for cancer-relevant protein–protein interaction (PPI) inhibitors. The model target is the TACC-3/Aurora-A mitotic complex, with additional PPIs including TPX-2/Aurora-A and BH3/BCL-2 family interactions to demonstrate broader applicability.
I will design aggregation-induced emission (AIE)-tagged peptide scaffolds that self-assemble into BMCs incorporating bioactive peptidomimetics to enable real-time visualization of condensate formation and intracellular distribution. Upon cancer cell uptake, the tumor-associated protease legumain will induce condensate disassembly, releasing the peptidomimetics. Longer term, this offers promise to release the peptidomimetic precisely at a tumor site while minimizing off-target exposure. The strategy will preserve the peptidomimetics’ bioactivity and ensure selective mitotic disruption or apoptosis leading to cell death. Key objectives include the synthesis of peptide–peptidomimetic hybrids, characterization of their binding kinetics (using biophysical tools such as ITC and fluorescence anisotropy) and cellular uptake, and quantification of spindle disruption and apoptosis markers (using imaging). By integrating image-guided delivery with enzyme-responsive release, this project goes beyond the state of the art, enabling enzyme-triggered, spatiotemporal control of intracellular delivery of unmodified peptidomimetics while preserving their bioactivity and offering a novel avenue for therapeutic intervention. The aligned additional training activities needed to deliver the project objectives will simultaneously elevate my research competences and profile ready for a position as a group leader in industry or academia.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2025-PF
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B15 2TT Birmingham
United Kingdom
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