Synthesis and evaluation of new theranostic agents for a breakthrough in neutron capture therapy

Targeted therapies are a major focus of cancer research today. Boron Neutron Capture Therapy (BNCT) is a binary therapy that uses the properties of boron-10 to deliver a high dose of radiation specifically to cancer cells. In BNCT, a patient is given a boron compound that targets cancer cells, he is then exposed to a beam of low-energy neutrons, which are taken by boron nuclei through a nuclear reaction called "capture" forming an excited 11-B atom. It releases analpha particle and Li ions, highly destructive to biological tissue in a short range, leading to cell death. BNCT has several potential advantages over other forms of cancer treatment, since the boron compound is selectively taken up by cancer cells, thus the radiation is delivered to tumor cells, minimizing damage to healthy tissues. Accelerators producing beams of low-energy neutrons for BNCT are already available in Japan, China, Finland, and others are being installed, and will support soon clinical trials and patient treatment. The main challenge for BCNT is the selective uptake of boron compounds by cancer cells and new targeting systems are urgently needed, requiring a strict collaboration between chemists and biologists. Moreover, a desirable property of the BNCT agent is the possibility of its monitoring in real time during the therapy, allowing the optimization of treatment planning. The Nano10-B project will focus on the incorporation of 10-B into nature-derived small molecules and nanoparticles to target the boron compound more effectively in cancer cells. Boron compounds will be planned to allow the introduction of 18-F, enabling the use of Positron Emission Tomography to follow the biodistribution of the compound, making these compounds potential theranostic agents. Finally, the project aims to develop new nanoparticle systems that can effectively deliver these compounds into tumor cells with high targeting and uptake efficacy through high drug-loaded silk fibroin nanoparticles (SFNs).