Tuning the oxidation of boron nitride for enhancing its antitumor activity

Abstract

A paramount challenge in orthopedic research is the design of next-generation multifunctional biomaterials that can simultaneously promote bone regeneration and treat pathological conditions, such as bone tumors. Here, we investigated hexagonal boron nitride (h-BN) as a mechanical reinforcement agent with intrinsic osteogenic and antitumor properties. We synthesized and chemically characterized three distinct h-BN materials: pristine h-BN (compound A), ball-milled h-BN (compound D2), and ball-milled and pyrolyzed h-BN (compound G2). Their comprehensive characterization confirmed that ball-milling and pyrolysis reduced particle size, lowered crystallinity, introduced high-density paramagnetic defects and dangling bonds, and incorporated oxygen-containing functional groups associated with the formation of hydrogen borate phases and boron oxynitride. Lattice destabilization and surface oxidation resulted in a ten-fold increase in boron release. Cytocompatibility profiling in human osteoblasts (hFOB1.19) and antitumor screening in osteosarcoma cell lines (U2OS and SaOS-2 cells) revealed that all h-BN compounds fully preserved osteoblast viability and enhanced their osteogenic differentiation. Moreover, h-BNG2, exhibited the most potent and selective dose-dependent antitumor effect. Mechanistically, this effect was driven by the increased intracellular reactive oxygen species generation that induced apoptosis, and by the modulation of key signaling pathways involved in cell death and bone differentiation, as validated by genome-wide transcriptomic analyses. Collectively, these findings show that h-BN physicochemical modification by ball-milling and pyrolysis optimizes boron flux and surface reactivity, establishing h-BNG2 as a highly promising candidate for advanced biomedical applications.

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BibTeX RIS

BibTeX

@article{souyris2026tuning,
  title = {{Tuning the oxidation of boron nitride for enhancing its antitumor activity}},
  author = {Lucas Souyris and Ingrid Charodin and Fanny Salmeron and Zahraa Saleh and Habib Belaid and David Cornu and Pierre-Yves Collart-Dutilleul and Mikhael Bechelany and Vincent Cavaillès},
  journal = {Biomedicine and Pharmacotherapy},
  year = {2026},
  month = sep,
  doi = {10.1016/j.biopha.2026.119593},
  url = {https://hal.umontpellier.fr/hal-05729285v1},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Tuning the oxidation of boron nitride for enhancing its antitumor activity
AU  - Lucas Souyris
AU  - Ingrid Charodin
AU  - Fanny Salmeron
AU  - Zahraa Saleh
AU  - Habib Belaid
AU  - David Cornu
AU  - Pierre-Yves Collart-Dutilleul
AU  - Mikhael Bechelany
AU  - Vincent Cavaillès
PY  - 2026
DA  - 2026/09/22
JO  - Biomedicine and Pharmacotherapy
DO  - 10.1016/j.biopha.2026.119593
UR  - https://hal.umontpellier.fr/hal-05729285v1
AB  - A paramount challenge in orthopedic research is the design of next-generation multifunctional biomaterials that can simultaneously promote bone regeneration and treat pathological conditions, such as bone tumors. Here, we investigated hexagonal boron nitride (h-BN) as a mechanical reinforcement agent with intrinsic osteogenic and antitumor properties. We synthesized and chemically characterized three distinct h-BN materials: pristine h-BN (compound A), ball-milled h-BN (compound D2), and ball-milled and pyrolyzed h-BN (compound G2). Their comprehensive characterization confirmed that ball-milling and pyrolysis reduced particle size, lowered crystallinity, introduced high-density paramagnetic defects and dangling bonds, and incorporated oxygen-containing functional groups associated with the formation of hydrogen borate phases and boron oxynitride. Lattice destabilization and surface oxidation resulted in a ten-fold increase in boron release. Cytocompatibility profiling in human osteoblasts (hFOB1.19) and antitumor screening in osteosarcoma cell lines (U2OS and SaOS-2 cells) revealed that all h-BN compounds fully preserved osteoblast viability and enhanced their osteogenic differentiation. Moreover, h-BNG2, exhibited the most potent and selective dose-dependent antitumor effect. Mechanistically, this effect was driven by the increased intracellular reactive oxygen species generation that induced apoptosis, and by the modulation of key signaling pathways involved in cell death and bone differentiation, as validated by genome-wide transcriptomic analyses. Collectively, these findings show that h-BN physicochemical modification by ball-milling and pyrolysis optimizes boron flux and surface reactivity, establishing h-BNG2 as a highly promising candidate for advanced biomedical applications.
SN  - 0753-3322
SN  - 1950-6007
ER  -

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