Evaluating the Boron Neutron Capture Therapeutic Threshold of Boron-Containing Carbon Dots in Diverse Tumor Cell Lines

Backgrounds Boron neutron capture therapy (BNCT) is a binary precision radiotherapy that selectively kills tumor cells via high-linear energy transfer α-particles from the 10B-neutron capture reaction, while preserving healthy tissues. Its efficacy is fundamentally limited by intracellular boron delivery efficiency. Boron-containing carbon dots (BCDs) are promising delivery agents with excellent biocompatibility, but systematic studies on their BNCT performance across diverse tumor types remain insufficient. Methods We evaluated BCDs in four tumor cell lines: U87-MG (glioblastoma), 4T-1 (breast cancer), HepG-2 (hepatocellular carcinoma), and B16-F10 (melanoma). We assessed dose-dependent cellular boron uptake via ICP-MS, cytotoxicity after thermal neutron irradiation via CCK-8 assay, and absorbed dose via Monte Carlo PHITS simulation, with statistical analysis by one-way ANOVA and Tukey's post-hoc test. Results BCDs showed concentration-dependent internalization with significant heterogeneous uptake across cell lines. U87-MG and 4T-1 had superior boron uptake and high BNCT sensitivity, while HepG-2 exhibited marked resistance (43-fold lower uptake than U87-MG), and B16-F10 showed moderate uptake. A critical therapeutic threshold was identified: significant cell killing only occurred when intracellular boron exceeded 20 μg B/mL with sufficient neutron fluence. Conclusion This study reveals the heterogeneous metabolic profiles of BCDs across different cancer types, and validates BCDs as a broad-spectrum radiosensitizing nanoplatform for BNCT. The identified critical intracellular boron therapeutic threshold provides a key reference for personalized dosimetry design and clinical translation of BCD-mediated BNCT.