Endophytic Nanoparticle: An Emerging Frontier in Biomedical, Agricultural, and Environmental Applications

Endophytic microorganisms that colonize plant tissues without causing harm serve as sustainable bio-factories for the green synthesis of metallic and metal-oxide nanoparticles. This review provides an integrated synthesis of endophytic diversity, biosynthetic mechanisms, and cross-sector applications, addressing the fragmentation in previous reports. Fungal endophytes particularly Aspergillus and Penicillium species and bacterial genera such as Bacillus and Streptomyces mediate nanoparticle formation, including silver, gold, zinc oxide, copper oxide, and selenium, through NADH-dependent reductase activity and metabolite-based bio-capping involving polyphenols, terpenoids, and alkaloids. Recent studies highlight Talaromyces funiculosus derived silver nanoparticles showing strong antibacterial zones (26 mm) and Penicillium verhagenii-produced selenium nanoparticles exhibiting selective anticancer cytotoxicity (IC₅₀ = 225–283 μg/mL) while sparing normal cells. We further discuss extracellular versus intracellular synthesis routes, correlations between synthesis parameters and particle size, morphology, and stability, and summarize biomedical, agricultural, and environmental applications using quantitative activity metrics. Statistical optimization tools including Taguchi and response-surface methodologies are emphasized for enhancing reproducibility and scalability. Finally, future directions involving metabolic engineering, OSMAC strategies to activate silent biosynthetic clusters, and omics-guided optimization are outlined. By linking mechanistic insights with translational outcomes, this review establishes endophyte-mediated nanotechnology as a scalable, eco-efficient platform addressing antimicrobial resistance, cancer therapy, food security, and environmental remediation.

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