The synthesis of small boron oxide nano particles (NPs) is reported. A sonochemical approach in the presence of a capping agent was employed to produce approximately 4-5-nm-sized B2O3 NPs, including the 1 B isotopically enriched form. The morphology and composition of the NPs were established using transmission electron microscopy and diffraction, respectively. X-ray photoelectron and Fourier transform infrared spectroscopies provided information about surface functionalization of the B2O3 NPs, which can be further modified through a facile, one-step ligand-exchange process. The toxicity of the synthesized NPs was investigated in Chinese hamster ovarian cells, indicating that these systems were nontoxic up to 1.7 mM concentrations.