Green-Synthesized Nanoparticles for Dual Targeting of Oral Biofilms and Oral Squamous Cell Carcinoma

Abstract

The co-evolution of multidrug resistance amongst oral pathogens and sub-par treatment outcomes associated with traditional OSCC therapy calls for alternative strategies, which not only differ in terms of the underlying mechanism but should also be biocompatible. One such strategy entails nanoparticle synthesis utilizing plant extracts as both reducing agents and ligands; secondary metabolic compounds endow the produced nanomaterials with unique biological activity. The aim of the present review is a comprehensive analysis of the preparation, characterization, and dual antibacterial/antitumorigenic activities of AgNPs, CuNPs, and FeNPs produced from aqueous extracts of Azadirachta indica and Syzygium cumini. The nucleation, growth kinetics, size distribution, and particle charge are all governed by the polyphenols content of aqueous plant extract; in particular, Syzygium cumini nanoparticles display monodispersity and low particle sizes (<20 nm) in comparison to larger Azadirachta indica nanoparticles that show enhanced stability due to the abundant presence of terpenoids. Amongst oral biofilm-forming bacteria, AgNPs have shown the greatest breadth of antimicrobial action at the minimum concentration range of 5-25 μg/mL; AgNPs showed greater than 90% biofilm inhibition whereas CuNPs showed antifungal efficacy against Candida albicans. FeNPs, though inherently less cytotoxic, offer a magnetically responsive platform for targeted drug delivery and localized hyperthermia. In OSCC cell lines, biogenic nanoparticles induced dose-dependent apoptosis through mitochondrial membrane depolarization, upregulation of the Bax/Bcl-2 ratio, cytochrome c release, and caspase-3 activation, with selectivity indices consistently superior to chemically synthesized counterparts — attributed to the modulation of oxidative thresholds by surface-adsorbed phytochemicals. Taken together, these phytometallic nanocomplexes represent a mechanistically integrated dual-action platform with potential translational relevance to precision oral therapeutics.