Sustainable Biosynthesis of Zinc Oxide Nanoparticles Using Carica papaya Fruit Metabolites: Anticancer Activity in Liver Cancer Models Supported by In Silico Modelling

Abstract

The present study investigated the sustainable biosynthesis of zinc oxide nanoparticles (ZnO-NPs) using Carica papaya fruit extract and evaluated their physicochemical properties and anticancer activity against hepatic cancer cells. The plant-mediated ZnO-NPs were synthesised through an environmentally friendly approach in which bioactive metabolites present in the fruit extract acted as reducing, stabilising, and capping agents. The synthesised nanoparticles were characterised using UV–visible spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, dynamic light scattering, and zeta-potential analysis to determine their optical properties, crystalline structure, surface functional groups, hydrodynamic size, and colloidal stability. The anticancer potential of the ZnO-NPs was assessed in liver cancer cells using cell-viability, reactive oxygen species, and redox-status assays. Treatment with the biogenic ZnO-NPs reduced cancer-cell viability in a concentration- and time-dependent manner and increased intracellular oxidative stress. The nanoparticles also altered antioxidant parameters, including glutathione, superoxide dismutase, catalase, and malondialdehyde, suggesting the involvement of redox imbalance in their cytotoxic activity. The selectivity of the nanoparticles was further evaluated by comparing their effects on cancerous cells. In addition, major C. papaya fruit metabolites, including quercetin, kaempferol, catechin, and chlorogenic acid, were subjected to molecular docking analysis against cancer-associated proteins, including epidermal growth factor receptor and glycogen synthase kinase 3 beta. These compounds demonstrated favourable interactions with the selected targets, supporting their possible contribution to the anticancer activity of the phytochemical-capped ZnO-NPs. Overall, the findings suggest that C. papaya fruit-mediated ZnO-NPs may represent a sustainable nanotherapeutic platform for hepatic cancer. Further mechanistic and in vivo studies are required to establish their therapeutic efficacy and safety.