Facile Sonochemically-assisted Bioengineering of Titanium Dioxide Nanoparticles and Deciphering Their Potential in Treating Breast and Lung Cancers: Biological, Molecular, and Computational-based Investigations

Combining sonochemistry with phytochemistry is a modern trend in the biosynthesis of metallic nanoparticles (NPs), which contributes to the sustainability of chemical processes and minimizes hazardous effects. Herein, titanium dioxide (TiO) NPs were bioengineered using a novel and facile ultrasound-assisted approach utilizing the greenly extracted essential oil of . FTIR and UV-Vis spectrophotometry were used to confirm the formation of TiO NPs. The X-ray diffraction (XRD) analysis showed the crystalline nature of TiO NPs. TEM analysis revealed the spherical morphology of the NPs with sizes ranging from 5.55 to 13.89 nm. Energy-dispersive X-ray (EDX) confirmed the purity of the greenly synthesized NPs. TiO NPs demonstrated outstanding antitumor activity against breast (MCF-7) and lung (A-549) cancer cells with estimated IC values of 1.73 and 4.79 μg mL. The TiO NPs were cytocompatible to normal cells (MCF-10A) with a selectivity index (SI) of 8.77 for breast and 3.17 for lung cancer. Biological assays revealed a promising potential for TiO NPs to induce apoptosis and arrest cells at the sub-G1 phase of the cell cycle phase in both cancer cell lines. Molecular investigations showed the ability of TiO NPs to increase apoptotic genes' expression (Bak and Bax) and their profound ability to elevate the expression of apoptotic proteins (caspases 3 and 7). Molecular docking demonstrated strong binding interactions for TiO NPs with caspase 3 and EGFR-TK targets. In conclusion, the greenly synthesized TiO NPs exhibited potent antitumor activity and mitochondrion-based cell death against breast and lung cancer cell lines while maintaining cytocompatibility against normal cells.