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Integrating Molecular Design and Cellular Dosimetry: Developing a Mechanistic Framework for Targeted Boron Neutron Capture Therapy


BASIC DATA OF THE RESEARCH PROJECT

  • ARIS code: N1-0495
  • TITLE: Integrating Molecular Design and Cellular Dosimetry: Developing a Mechanistic Framework for Targeted Boron Neutron Capture Therapy
  • PRICE CLASS: B
  • PROJECT LEADER: Martin Gazvoda, PhD
  • LEADING ORGANISATION: Faculty of Chemistry and Chemical Technology, University of Ljubljana
  • PROJECT LEADER AT INSTITUTE OF ONCOLOGY: Prof. Maja Čemažar, PhD
  • DURATION: 1.9.2026 – 31.8.2029
  • FINANCING: Slovenian Research and Innovation Agency

SHORT SUMMARY:

Boron neutron capture therapy (BNCT) has long been envisioned as a tumor-selective radiation modality; however, its broader clinical implementation remains limited. We posit that this stems from an insufficient mechanistic understanding of this binary therapeutic concept at the cellular level. This project aims to establish a mechanistic foundation for BNCT by defining how intracellular boron concentration and localization determine therapeutic efficacy. We hypothesize that precise spatial control of boron delivery within cancer cells is the key to effective and selective alpha-particle–mediated cytotoxicity. To test this, we will develop next-generation boron-rich biologics designed for efficient and selective intracellular delivery, generating a focused library of optimized constructs. Their biological activity and delivery efficiency will be evaluated in cellular and physiological systems, to ensure clinically relevant characterization. A central component of the project is the close integration of molecular design with theoretical modeling. The design of boron-rich biologics will be guided by Monte Carlo simulations of BNCT at the cellular level, enabling prediction of how boron distribution influences therapeutic outcome. These insights will be coupled with experimental validation in irradiated cancer cell models to refine and optimize boron-delivery strategies. The most promising boron-rich agent will be advanced to early in vivo evaluation to assess toxicity, biodistribution, and antitumor activity. By bridging molecular engineering and radiation physics, this proposal aims to establish the mechanistic understanding necessary to advance BNCT into a rationally designed targeted alpha-radiation strategy for cancer therapy.