Boron Nitride: The Silent Guardian of Health

Nanotechnology is a field that involves the manipulation of materials at the nanoscale, including the scientific principles employed in this process and the new material properties and development prospects discovered at this scale. Nanotechnology has been applied to various aspects of medicine, including drug delivery, tumor diagnosis and treatment, imaging, and antibacterial agents. Changes in the scale of nanomaterials can lead to significant variations in their surface physical and chemical properties. In recent years, with the advancement of nanotechnology, boron nitride (BN) with a graphitic structure has emerged as an innovative medical material, demonstrating potential applications in anticancer properties, antibacterial effects, and as a drug carrier.

1.Boron nitride nanomaterials

Boron nitride is a layered molecular crystal composed of boron from group III and nitrogen from group V, exhibiting a hexagonal regular network structure. Within the layers of the molecular crystal, boron and nitrogen atoms are bonded through coordination bonds, which are very strong, resulting in a tight combination of B and N atoms within the layers. Interlayer connections are made via van der Waals bonds, which are weaker, making it easy for layers to detach from one another. Based on different crystal types, the crystal structure of boron nitride can be classified into four categories: hexagonal boron nitride (h-BN), cubic boron nitride (c-BN), wurtzite boron nitride (w-BN), and rhombohedral boron nitride (r-BN), among which hexagonal boron nitride (h-BN) has the most extensive applications.Hexagonal boron nitride (h-BN), as a highly significant inorganic material, possesses a structure similar to that of graphite and appears as a white powder, hence it is also referred to as 'white graphite.' Nano-sized h-BN can encapsulate to form zero-dimensional boron nitride nanoparticles (BNNPs), coalesce to form one-dimensional boron nitride nanotubes (BNNTs), and be exfoliated to create two-dimensional boron nitride nanosheets (BNNs) and boron nitride nanoribbons (BNNRs). Each of these nanostructures exhibits unique superior properties, such as high specific surface area, large bandgap energy, low dielectric constant, excellent thermal stability, chemical stability, and outstanding biocompatibility.

2.Properties of Boron Nitride

In various types of boron nitride crystals, researchers have predominantly focused on h-BN and c-BN due to their superior properties.

The layered structure and lattice parameters of h-BN are similar to those of graphite. The nitrogen and boron atoms within each layer are held together by strong sp2 covalent bonds and dipole interactions, which result in a high melting point for h-BN, along with excellent high-temperature and refractory capabilities. In contrast, the interlayer bonding in h-BN is facilitated by weaker van der Waals forces, allowing for easy sliding between layers, making it suitable for use as a lubricating material. Additionally, h-BN possesses a bandgap of up to 5.97 eV, which provides exceptional insulating properties even at elevated temperatures. In summary, the main characteristics of h-BN include a high melting point, high thermal conductivity, good lubricating properties, high mechanical strength, good chemical stability, excellent dielectric performance, and good biocompatibility. However, the dispersion of h-BN in water is poor; thus, functionalizing h-BN materials to improve their dispersion will be beneficial for further applications in the Biomedical field.

c-BN features a sphalerite structure and belongs to the face-centered cubic crystal system, making it a new type of superhard material with a structure similar to that of diamond. c-BN exhibits extremely high thermal conductivity, thermal stability, and chemical stability, among other properties. In 2009, scholars first identified natural c-BN in nature, naming it chaozhuite, yet the c-BN single crystals used industrially today are still synthesized artificially, using h-BN as the precursor under high temperature and pressure.

3.Boron nitride in the biomedical field

BN exhibits good biocompatibility both in vitro and in vivo, possessing properties comparable to or even superior to graphene-based materials in biological applications. It can be utilized in various fields such as antibacterial applications, drug delivery, boron delivery agents, tissue engineering, and in vivo imaging.

• Antibacterial：Recently, studies have found that boron nitride nanosheets exhibit effective antibacterial properties against antibiotic-resistant bacteria (AMR), demonstrating good biocompatibility without causing secondary resistance during long-term use. Kivanc et al. investigated the antibacterial and antibiofilm activity of h-BN nanoparticles against Streptococcus thermophilus 3.3, Staphylococcus pasteuri M3, Candida sp. M25, and Streptococcus thermophilus ATCC 25175. The toxicity of h-BN nanoparticles on human normal skin fibroblasts and Madin-Darby canine kidney cells was assessed using MTT, SRB, and Pico Green assays to measure cell viability. The experiments indicated that h-BN nanoparticles have a significant inhibitory effect on bacterial growth.
• Drug delivery：h-BN is also regarded as a highly promising drug carrier. Cheng et al. synthesized hexagonal boron nitride nanosheets (BNNSs) in bulk using a salt template method, which effectively inhibited the proliferation of breast cancer in both in vivo and in vitro experiments, indicating the potential of BNNSs in drug delivery applications. Research has demonstrated that using spherical BN as a carrier, deoxyribonucleic acid-loaded brain natriuretic peptide penetrates tumor IAR-6-1 cells through endocytosis, subsequently releasing DOX into the cytoplasm and nucleus, thereby specifically targeting and killing cancer cells.
• Tissue Engineering：In the field of dental materials, Lee et al. prepared BNNs using high-energy ball milling and dispersed them in a Zirconia matrix, followed by plasma sintering to consolidate the composite powder. The zirconia with the addition of BNNs demonstrated an increase in strength of up to 27.3% and an improvement in fracture toughness of 37.5%, while also inhibiting the degradation of the zirconia matrix in humid environments, demonstrating the potential value of BNNs as reinforcing materials for dental applications. Degrazia et al. found that the addition of 0.15 wt.% of BNNTs improved the chemical and mechanical properties of dental composite resins and promoted mineral deposition, contributing to the prolongation of the lifespan of dental restorations.
• Boron delivery agent：Boron nitride nanomaterials, due to their high boron content and low cytotoxicity, can serve as boron delivery agents for boron neutron capture therapy (BNCT). BNCT is a novel specific radiotherapy method that targets and kills cancer cells without harming normal cells. Polyethylene glycol-modified boron nitride nanotubes have been shown to act as boron delivery agents for BNCT, with boron accumulation in B16 melanoma cells being approximately three times that of the second-generation boron delivery agent BSH (sodium borane thiosulfate). Boron nitride nanotubes modified with poly-L-lysine and folic acid are selectively uptaken by polymorphic glioblastoma cells after coupling with fluorescent quantum dots, thus serving both as boron delivery agents for BNCT and allowing for the tracking of intracellular drug behavior. Boron nitride nanospheres have also been reported to serve as a high-quality boron reservoir for the treatment of prostate cancer, where controllable crystalline boron can be released sustainably, thereby reducing prostate cancer cell viability and inducing apoptosis. In situ tumor models have confirmed the in vivo anticancer efficacy of hollow boron nitride spheres.

Summary

Boron nitride is an excellent inorganic non-metallic material that can exist in four different crystal structures, the most common of which are h-BN and c-BN. In recent years, h-BN materials have gradually attracted attention as structural analogs of graphene, due to their superior biocompatibility and higher chemical stability, suggesting that h-BN has the potential to replace carbon nanostructures in biomedical applications. Owing to its unique structure and properties, BN has a very broad range of applications. However, research on BN in the field of biomedicine is still in its infancy and merits further exploration.