Nanodiagnostics and nanotoxicology: A systematic review and meta-analysis on nanoparticle applications and safety in metabolic organs

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Nanotechnology is reshaping the biomedical landscape by offering unprecedented capabilities in disease diagnostics, targeted therapy, and biosensing. Nanoparticles (NPs), owing to their unique physicochemical properties, enable ultra-sensitive biomarker detection, real-time monitoring, and minimally invasive assays across oncology, infectious diseases, and neurology. However, their biological interactions also raise significant concerns regarding organ-specific toxicity, particularly in metabolic systems. This systematic review and meta-analysis aim to integrate current evidence on nanoparticle-based diagnostic applications with emerging insights into their toxicological impacts on key metabolic organs — liver, kidney, pancreas, spleen, and adipose tissue. It further examines mechanistic pathways, dose-dependent effects, and translational challenges to bridge the gap between innovation and biosafety. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar from January 2015 to October 2025 following PRISMA 2020 guidelines. Eligible studies reported quantitative diagnostic performance metrics (e.g., limit of detection, sensitivity, multiplexing capacity) or biological outcomes (e.g., oxidative stress, apoptosis, fibrosis, endocrine disruption) related to NP exposure. Meta-analytic synthesis was performed on 42 studies reporting comparable quantitative toxicity data. Diagnostic applications of metallic, polymeric, photonic, and hybrid nanoparticles demonstrated up to a 1000-fold improvement in sensitivity over conventional assays, with mean detection limits reaching the femtomolar range. However, pooled toxicity analysis revealed significant organ-specific risks: hepatic ROS generation (standardized mean difference [SMD] = 1.42, 95% CI: 1.10–1.75), renal tubular apoptosis (SMD = 1.27, 95% CI: 0.94–1.61), and β-cell impairment (SMD = 1.18, 95% CI: 0.88–1.49). Translational challenges remain due to poor clearance kinetics, chronic inflammation, and incomplete regulatory frameworks. Nanoparticles hold transformative potential in precision diagnostics, but their clinical adoption demands a nuanced understanding of toxicological trade-offs. Future research must focus on biodegradable and renal-clearable materials, mechanistically guided design strategies, standardized toxicological protocols, and AI-driven predictive models. This review provides a dual-perspective framework that integrates diagnostic breakthroughs with biosafety imperatives, guiding the next phase of nanomedicine toward safe and effective clinical translation.

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