Enhancing Boron Neutron Capture Therapy (BNCT) with Materials Based on COSAN-Functionalized Nanoparticles

<b>Background/Objectives</b>: Boron neutron capture therapy (BNCT) is a promising approach for selectively targeting and destroying malignant cells using ¹⁰B isotopes. A significant challenge in BNCT lies in the development of efficient boron delivery systems that ensure adequate boron accumulation within tumor cells. This study aims to synthesize, characterize, and evaluate COSAN-functionalized nanoparticles (<b>NP@I-COSAN</b>) as a potential boron carrier for BNCT. <b>Methods</b>: Hybrid nanoparticles were synthesized by conjugating monoiodinated cobaltabisdicarbollides (<b>I-COSAN</b>) to commercially available acrylic polymer-based nanoparticles. Functionalization and cellular uptake were confirmed through FTIR, TGA, UV-Vis spectroscopy, and TEM/EDX analyses. Biocompatibility was evaluated by assessing cytotoxicity in HeLa cells and <i>C. elegans</i> as an in vivo model. Intracellular boron uptake was quantified using ICP-MS, with results compared to those obtained with 4-borono-L-phenylalanine conjugated to fructose (<b>f-BPA</b>). An in vitro BNCT proof-of-concept assay was also performed to evaluate therapeutic efficacy. <b>Results</b>: <b>NP@I-COSAN</b> demonstrated low cytotoxicity and efficient internalization in cells. ICP-MS analysis revealed stable boron retention, comparable to traditional boron agents. The BNCT assay further showed that <b>NP@I-COSAN</b> was effective in inducing tumor cell apoptosis, even at lower boron concentrations than conventional treatments. <b>Conclusions</b>: These results underscore the potential of <b>NP@I-COSAN</b> as an effective boron delivery system for BNCT, offering a promising strategy to enhance boron accumulation within tumor cells and improve treatment efficacy.