Synergistic Action of Vanillic Acid‐Coated Titanium Oxide Nanoparticles: Targeting Biofilm Formation Receptors of Dental Pathogens and Modulating Apoptosis Genes for Enhanced Oral Anticancer Activity

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Abstract
The prevalence of bacterial and fungal infections is caused by S. aureus, S. mutans, E. faecalis, and Candida albicans are often associated with dental illnesses. In the present study, a unique strategy was used to combat these diseases by fabricating titanium dioxide nanoparticles (TiO2 NPs) conjugated with the plant‐based molecule vanillic acid (VA). To confirm the structural characterization of the synthesized VA‐TiO2 NPs, an extensive analysis was carried out utilizing methods such as SEM, FTIR, and XRD. Assessments for scavenging reactive oxygen species were performed to evaluate its antioxidant capability. Furthermore, a zone of inhibition test targeting pathogenic oral bacteria was used to assess the antibacterial efficacy of VA‐TiO2 NPs. Molecular modeling investigations were performed to better understand the interactions among vanillic acid and dental pathogen receptors using the Autodock program. The findings indicated that VA‐TiO2 NPs exhibited strong free radical scavenging activity. Additionally, they showed excellent antibacterial action towards dental pathogens, with a minimum inhibition level of 60 μg/mL. Furthermore, at doses of 15 μg/mL, 30 μg/mL, 60 μg/mL, and 120 μg/mL, VA‐TiO2 NPs demonstrated concentration‐dependent apoptotic impacts on human oral carcinoma cells. Apoptotic gene over‐expression was identified by the molecular perspectives that revealed the anticancer mechanism of VA‐TiO2 NPs on KB cells. This study highlights the promising suitability of VA‐TiO2 NPs for dental applications due to their robust antioxidant, anticancer, and antimicrobial characteristics. These nanoparticles present an evident prospect for addressing oral pathogen challenges and improving overall oral health.

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