A Nano-Omics Framework for Nanotoxicological Evaluation of Green-Synthesized Nanoparticles and Nanosafety

Nanotechnology enables the manipulation of materials at dimensions comparable to biomolecules, offering transformative applications across medicine, agriculture, and environmental systems. Among emerging nanomaterials, green-synthesized nanoparticles (GSNPs) have attracted considerable attention due to their eco-friendly production, biogenic surface functionalization, and potential for improved biocompatibility. However, despite reduced process-related toxicity, GSNPs pose unique safety challenges arising from nanoscale properties, dynamic protein corona formation, and complex nano-bio interactions that are inadequately captured by conventional toxicity assays. This review critically evaluates the relevance of nano-omics as a next-generation toxicological tool for hazard identification and risk assessment of emerging nanomaterials, examines the limitations of traditional bioassays, and highlights the growing role of nano-omics approaches, including transcriptomics, proteomics, metabolomics, lipidomics, and epigenomics, in providing systems-level insights into GSNP-induced biological responses. These approaches reveal pathway-level perturbations, such as oxidative stress, immune modulation, metabolic reprogramming, and epigenetic alterations, even at subcytotoxic exposure levels. We further discuss how surface chemistry, protein corona evolution, and intracellular trafficking govern the biological identity and fate of GSNPs. Current limitations in nano-omics, including the lack of standardized protocols, data integration challenges, and regulatory gaps, are critically addressed. An integrative multi-omics framework aligned with FAIR data principles is proposed to support predictive nanosafety assessment and safe-by-design development of green nanomaterials.