Glioblastoma multiforme (GBM), a deadly brain cancer, remains incurable due to its deep location and resistance to conventional therapies like photodynamic therapy (limited by light penetration) and neutron-based Capture Therapies (challenged by tumor specificity). The NuCapCure project introduces two groundbreaking approaches:
1. NuCapCure Proton combines proton radiotherapy’s precision with protondynamic therapy (activating photosensitizers via protons) and proton capture therapy (generating three alpha particles per proton interaction) for localized, multi-mechanistic tumor destruction.
2. NuCapCure Neutron enhances the efficacy of conventional neutron capture therapiesby integrating neutron-activated photosensitizers (from the FRINGE project) to improve tumor targeting and efficacy.
Both strategies exploit engineered compounds using intracellular biosynthesis to produce custom therapeutic agents in situ, aiming to overcome drug delivery barriers. The project unites experts across proton/neutron physics, synthetic chemistry, radiobiology, and oncology to pioneer targeted, curative treatments for GBM and other intractable cancers.
The overarching goal of NuCapCure is the development of two radical, multimodal anticancer treatments, very specific to GBM, via the formation of bespoke PSs using intracellular biochemistry: A treatment combining proton radiotherapy, proton capture therapy and proton-induced PS activation.
The specific project objectives are:
• Design, development, validation and optimisation of NuCapCure bespoke prodrugs for the intracellular production of modified PSs.
• Initial photophysical characterization and conventional PDT studies on the various NuCapCure compounds in cell cultures (WP2).
• In-vitro validation and optimisation of the NuCapCure treatments in 2D and 3D GBM cell cultures. Selection of the best in-vitro performing PSs for subsequent in-vivo studies (WP3).
• In-vivo validation of NuCapCure efficacy, on GBM preclinical tumour models (WP4).
If successful NuCapCure could provide:
• A significant clinical advancement by offering curative solutions to currently incurable cancer indications
• New avenues in using cells for bespoke intracellular synthesis
• A boost to the European and international medical business sector by creating new therapies and hence new employment and marketing opportunities.
