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Tunable Radiolabelled Agents based on Molecular Cages for Theranostics

Project description

Modular radiolabelled molecular cages as next-generation theranostic agents

Prostate cancer is the second most diagnosed cancer in men, with high mortality. Current treatments often lack specificity and are highly toxic. Theranostic agents – systems that enable diagnostic imaging and targeted therapeutic functions in a single platform – are a promising alternative. With the support of the Marie Skłodowska-Curie Actions programme, the TRACE project aims to pioneer a new generation of theranostic agents based on modular molecular cages, engineered to simultaneously carry targeting units, therapeutic and imaging radionuclides, and fluorescent probes. These innovative architectures will enable precise, multimodal imaging alongside targeted radiotherapy of prostate cancer cells, with superior stability and binding affinity, providing versatile platforms potentially adaptable to other cancer types.

Objective

Prostate cancer (PC) is the second most commonly diagnosed cancer in men and a leading cause of mortality. Current systemic therapies, particularly chemotherapy, often suffer from high toxicity and limited specificity. Theranostic agents, which combine diagnostic and therapeutic functions in a single platform, enable targeted imaging and treatment when equipped with units that recognize specific biomarkers, offering a promising alternative to conventional approaches. In PC, the prostate-specific membrane antigen (PSMA) is a validated target, with PSMA-617 already in clinical use. However, its rigid molecular design hinders multimodal integration, requiring separate administration of diagnostic and therapeutic agents. TRACE proposes an ambitious and ground-breaking strategy to overcome these limitations through the design of multifunctional molecular cages (MCs) as next-generation theranostic agents. This project will pioneer a modular post-functionalization strategy to introduce multiple units of PSMA target ligands, DOTA macrocycle chelators, therapeutic radionuclides (^177Lu), imaging radionuclides (^64Cu), and fluorescent probes within a single and robust MC architecture. This innovative MC design will allow precise control over multifunctionality, enhanced binding affinity, synergistic therapy, multimodal imaging, and superior biological stability. Importantly, the intrinsic coordination properties of the MCs will allow confinement and stabilization of imaging radionuclides in biological media, improving diagnostic accuracy. TRACE will deliver the first family of covalent MC-based theranostic agents for PC, providing superior selectivity, stability, and therapeutic efficacy. Beyond prostate cancer, this versatile supramolecular platform will pave the way for personalized cancer treatment.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITAT ZURICH
Net EU contribution
€ 292 118,88
Address
RAMISTRASSE 71
8006 Zurich
Switzerland
Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data