Boron nitride nanotubes (BNNTs) have emerged as promising candidates for boron neutron capture therapy (BNCT) due to their unique combination of neutron absorption capability and intrinsic infrared photoluminescence. BNCT is a targeted radiotherapy that relies on the nuclear capture reaction between thermal neutrons and boron-10 (10B), producing high-energy alpha particles and lithium nuclei that destroy tumor cells while sparing surrounding healthy tissue. The integration of BNNTs into this therapeutic approach offers advantages in both delivery and tracking, addressing key challenges in the field.
The neutron absorption cross-section of 10B is significantly high at 3837 barns for thermal neutrons, making it ideal for BNCT. BNNTs naturally incorporate boron, but their effectiveness depends on the isotopic enrichment of 10B. Enrichment methods include chemical vapor deposition (CVD) using 10B-enriched precursors, such as 10B2H6 or 10BCl3, which can yield BNNTs with 10B concentrations exceeding 95%. Alternatively, isotopic separation via centrifugation or laser-assisted techniques can be employed before synthesis. The enriched BNNTs exhibit enhanced neutron capture efficiency, directly influencing the therapeutic outcome.
Tumor accumulation is a critical factor for successful BNCT. Studies have demonstrated that functionalized BNNTs can selectively accumulate in tumor tissues through passive targeting via the enhanced permeability and retention (EPR) effect or active targeting using tumor-specific ligands. Surface modifications with polyethylene glycol (PEG) improve biocompatibility and prolong circulation time, while conjugation with antibodies or peptides enhances tumor specificity. In vivo studies using murine models have shown that intravenously administered BNNTs achieve tumor-to-normal tissue boron concentration ratios of 3:1 or higher, meeting the clinical threshold for effective BNCT.
Neutron beam dosimetry is another crucial aspect of BNCT. The therapeutic effect depends on the thermal neutron flux, which must be optimized to ensure sufficient boron neutron capture reactions without excessive damage to healthy tissue. The required thermal neutron flux typically ranges from 1x10^8 to 5x10^8 neutrons/cm²·s, with a fluence of approximately 1x10^12 neutrons/cm² per treatment session. Beam shaping and filtering are necessary to achieve the appropriate energy spectrum, as epithermal neutrons (0.5 eV to 10 keV) are preferred for deep-seated tumors due to their longer penetration depth and subsequent thermalization in tissue.
One of the standout features of BNNTs is their intrinsic infrared photoluminescence, which enables real-time tracking and biodistribution analysis. Unlike conventional fluorescent labels, BNNTs do not photobleach or exhibit toxicity associated with organic dyes or quantum dots. Their emission in the near-infrared (NIR) region (700-1100 nm) allows for deep tissue imaging with minimal autofluorescence interference. This property facilitates non-invasive monitoring of BNNT accumulation in tumors, ensuring accurate dosimetry and treatment planning.
The combination of neutron absorption and photoluminescence in BNNTs presents a theranostic platform that integrates therapy and diagnostics. Pre-treatment imaging confirms tumor targeting, while post-treatment assessment verifies therapeutic delivery. This dual functionality reduces the reliance on separate contrast agents, simplifying the clinical workflow and improving patient outcomes.
Safety and biocompatibility are paramount for clinical translation. Toxicity studies have shown that properly functionalized BNNTs exhibit low systemic toxicity and are gradually cleared via renal and hepatobiliary pathways. However, long-term biodistribution and retention studies are ongoing to ensure no adverse effects. The stability of BNNTs under physiological conditions further supports their use, as they resist degradation in the harsh tumor microenvironment.
In summary, BNNTs represent a multifunctional nanomaterial for BNCT, combining efficient neutron absorption with built-in tracking capabilities. Advances in 10B enrichment, tumor-targeting strategies, and neutron beam optimization are critical to harnessing their full potential. The inherent infrared photoluminescence of BNNTs provides a unique advantage for real-time monitoring, enhancing precision and efficacy. As research progresses, BNNT-based BNCT could become a mainstream option for targeted cancer therapy, offering improved selectivity and reduced side effects compared to conventional treatments.