A Multimodal Approach of Beta-Sitosterol-Coated Zinc Oxide Nanoparticles for Combating Oral Pathogens and Oral Cancer

Abstract

Oral health problems such as infections, tooth decay, and gum disease, often caused by oral pathogens, are increasingly linked to oral cancer. This study successfully synthesized and characterized beta sitosterol functionalized ZnO nanoparticles (BS ZnO NPs), with UV-Visspectroscopy showing a prominent absorption peak at 302 nm, and FTIR analysis confirming the functionalization through characteristic peaks of O–H, C=C, C–O, and Zn–O bonds. SEM and XRD analyses revealed their crystalline nature and morphology. The antioxidant potential of BS-ZnO NPs, demonstrated through DPPH and ABTS assays, showed a dose-dependent radical scavenging activity comparable to standard antioxidants. Antimicrobial activity against Streptococcus aureus, Enterococcus faecalis, Candida albicans, and Staphylococcus mutans revealed significant growth inhibition and superior efficacy to amoxicillin at equivalent concentrations. Molecular docking studies highlighted strong binding affinities of BS with pathogen virulence proteins, including Als3 adhesin in C. albicans and phospholipase C in S. aureus, disrupting biofilm formation and microbial adhesion. Additionally, BS-ZnO NPs exhibited potent anticancer activity against KB oral cancer cells, reducing cell viability to 28% at 100 μg/mL and outperforming cyclophosphamide. Gene expression analysis showed significant downregulation of the anti-apoptotic gene Bcl-2 and upregulation of pro-apoptotic Bax and tumor suppressor p53, highlighting their role in modulating apoptotic pathways. These findings underscore the multifunctional potential of BS-ZnO NPs as promising agents for oral health applications, including antioxidants, antimicrobials, and targeted therapeutics for oral cancer.