Background/Objectives: 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 (NP@I-COSAN) as a potential boron carrier for BNCT. Methods: Hybrid nanoparticles were synthesized by conjugating monoiodinated cobaltabisdicarbollides (I-COSAN) 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 C. elegans 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 (f-BPA). An in vitro BNCT proof-of-concept assay was also performed to evaluate therapeutic efficacy. Results: NP@I-COSAN 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 NP@I-COSAN was effective in inducing tumor cell apoptosis, even at lower boron concentrations than conventional treatments. Conclusions: These results underscore the potential of NP@I-COSAN as an effective boron delivery system for BNCT, offering a promising strategy to enhance boron accumulation within tumor cells and improve treatment efficacy.

Background: Boron neutron capture therapy (BNCT) is a binary modality based on the nuclear reaction ¹⁰B (n, α) lithium-7 (⁷Li) that has been used to treat a variety of tumors, among these, cutaneous melanoma (CM). In previous boron biodistribution studies in agreement with the personalized oncology, we have demonstrated that boronophenylalanine (BPA) uptake can be correlated with the tumoral temperature and viability. The main aim of these studies was to evaluate the relationship between tumoral temperature and the response to the complete BNCT. Methods: Nude mice were implanted with human melanoma cells (Mel J) and divided into different groups (Control, NCT, BNCT I and BNCT II) and irradiated with the thermal neutron beam from RA-6 (4.96×10⁸/cm²/sec) during 37 and 55 minutes respectively. Tumor and body temperatures were measured by Static Infrared Imaging (SIRI), and it was performed the following up of the animals. Results: Tumor growth showed a complete growth inhibition during the first 20 days after treatment in both BNCT groups (BNCT I and BNCT II vs. Control P<0.001). Considering the analogy between the Fourier’s Law of Heat Conduction and the Ohm’s law of Electrical Conduction, the quantity (T_tum-T_inf)/(T_body-T_tum) was analyzed as a function of Vf/Vi (Final volume/Initial volume) ratio. A tendency to higher values of the temperature’s ratios, was observed with respect to the degree of tumor control (BNCT I with a R² of 0.3527, BNCTII with a R² of 0.3327) in agreement with previous boron biodistribution studies. The histology and immunohistochemical studies showed larger areas of necrosis and picnotic regions and a significant decrease of the Ki-67 antibody labeling in the BNCT II group evidencing important tumor damage. Conclusions: tumoral characteristics, especially the temperature, could be used to plan a personalized treatment for each patient. As values of correlation between temperature and tumoral response showed to be weak, we considered to explore a new model of three dimension for heat transport process.