Green Synthesis and Surface Functionalization of Nanoparticles for Targeted Drug Delivery and Antimicrobial Applications

Abstract

   Green synthesis of nanoparticles using plant extracts, microbial agents, and bio-derived templates has emerged as a paradigm-shifting approach in nanomedicine, offering an eco-compatible alternative to conventional physicochemical fabrication methods. This study presents a systematic investigation into the green-route synthesis of silver (AgNPs), gold (AuNPs), zinc oxide (ZnO-NPs), and polymeric nanoparticles employing Azadirachta indica leaf extract, Camellia sinensis polyphenols, and Curcuma longa rhizome extract as reducing and capping agents. Optimized synthesis conditions yielded monodisperse nanoparticles with mean hydrodynamic diameters of 18.4 ± 2.1 nm (AgNPs), 22.7 ± 1.9 nm (AuNPs), and 35.3 ± 3.4 nm (ZnO-NPs), confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Surface functionalization was achieved through sequential conjugation of polyethylene glycol (PEG), folic acid (FA), and carboxymethyl chitosan (CMC) to engineer active-targeting vectors. In vitro drug loading studies demonstrated encapsulation efficiencies of 89.2% and 91.7% for doxorubicin (DOX) and curcumin, respectively. pH-responsive drug release profiles showed 78.3% cumulative DOX release at pH 5.0 (tumour microenvironment) versus 21.4% at pH 7.4 over 72 hours, indicating strong pH-gated behaviour. In vitro cytotoxicity assays on MCF-7 breast cancer cells revealed IC₅₀ values of 0.38 µg/mL for FA-PEG-AuNP-DOX conjugates compared to 2.74 µg/mL for free DOX. In vivo biodistribution studies in BALB/c mice bearing xenograft tumours demonstrated 4.2-fold higher tumour accumulation of functionalized nanoparticles relative to non-targeted controls, with haematological and histopathological analyses confirming negligible systemic toxicity. These results collectively establish green-synthesized, surface-functionalized nanoparticles as highly promising theranostic platforms for precision oncology.