Metabolomics-Guided Green Nanomedicine: Phytochemical-Mediated Metal and Metal Oxide Nanoparticles Toward Precision Cancer Therapy

Cancer remains a major global health challenge, and despite advances in chemotherapy, radiotherapy, immunotherapy, and targeted therapy, treatment outcomes are still limited by systemic toxicity, poor tumor selectivity, multidrug resistance, and inadequate efficacy against advanced disease. Nanotechnology has emerged as a promising strategy to address these limitations by improving drug delivery, imaging, radiosensitization, and immunomodulation. Among nanomaterials, phytochemical-mediated metal and metal oxide nanoparticles have attracted increasing interest as sustainable and potentially biocompatible alternatives to conventionally synthesized systems. However, their development remains constrained by poor reproducibility, lack of mechanistic understanding, and limited clinical translational progression, mainly because of the chemical complexity of plant extracts. In this review, we critically examine the role of metal nanoparticles in oncology, and we compare their anticancer mechanisms. We further evaluate phytochemical-mediated nanoparticle synthesis by discussing how plant-derived metabolites influence reduction, nucleation, capping, and the resulting physicochemical properties that influence biological activity. We argue that metabolomics offers a critical framework for overcoming one of the major limitations of green nanotechnology by enabling the comprehensive chemical characterization of plant extracts, identification of metabolites associated with nanoparticle formation, and correlation of metabolite profiles with nanoparticle physicochemical properties and anticancer activity. The integration of metabolomics with nanoparticle characterization could contribute to the advancement of green synthesis from empirical extract-based fabrication, toward a more predictive, standardized, and mechanistically informed nanoparticle design. Finally, we discuss the major barriers to clinical translation, including batch-to-batch variability, bio-corona effects, biodistribution, long-term toxicity, and regulatory compliance. Overall, the integration of metabolomics with phytochemical-mediated nanoparticle synthesis represents an emerging strategy for improving chemical characterization, mechanistic understanding, and reproducibility, with potential future relevance to the development of more rationally designed nanomedicines for precision oncology.