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.