Boron nitride nanostructures as effective adsorbents for melphalan anti-ovarian cancer drug. Preliminary MTT assay and in vitro cellular toxicity

Abstract

Boron nitride (BN) is an interesting material and has attracted the attention of many scholars in the last decade due to its surprising properties. Herein, a simple and inexpensive method is disclosed for the preparation of hexagonal boron nitride and the synthesized nanosheets are characterized by means of FT-IR, SEM, TEM, XRD, TGA and XPS. Then, the fabricated nanostructure is subjected to the delivery of melphalan anti-cancer drug to attain ~42% loading. After that, density functional theory (DFT) calculations are performed to study the adsorption and detection of melphalan anti-cancer drug on the surface of pure and Mg, C, Al, Si, Ge, and Ga doped boron nitride nanostructures by using B3LYP and B3PW91 functionals. The doped XB11N12 nanostructures facilitate adsorption of melphalan compared to the pristine B12N12 by increasing the electrophilicity and chemical hardness of the doped nanoparticles. However, the B3PW91 functional gives rise to both higher adsorption energy and energy gap difference compared to B3LYP functional. In addition, the PCM and SMD calculations show that the selected adsorption complexes are stable in the water phase, as a preferred medium for the in vivo conditions. Furthermore, the computations show greater sensitivity of GeB12N12 to the presence of melphalan, therefore, this nanostructure can be regarded as a suitable sensor for detection of melphalan anti-cancer drug in biological systems. Finally, the in vitro cellular toxicity and viability of GeB12N12 nanoparticles was examined on OVCAR-3 cancer cells. The inhibitory dose ID50 of GeB12N12 nanoparticles confirmed that this material can be achieved as an acceptable vehicle for delivery of melphalan. Moreover, the effect of GeB12N12 nanoparticles (15 μg/mL) on the average growth curves of OVCAR-3 cancer cells showed a decrease of the MTT signal compared to the untreated cells and GeB12N12 can reduce the metabolic activity of the performed cancer cells.