Nanoparticles and their significant risks: a comprehensive review of toxicological and regulatory perspectives

Abstract Background Nanoparticles are increasingly important as drug carriers due to their ability to enhance solubility, stability, and selective delivery of therapeutic agents, enabling accumulation at disease sites, interaction with cell-surface receptors, and penetration of biological barriers such as the blood-brain barrier. Despite these numerous advantages, their potential toxicity remains a key obstacle to safe clinical use. Emerging evidence suggests that nanoparticles may alter the composition of the gut microbiome, potentially affecting metabolism, immune homeostasis, neurobehavioral pathways, and reproductive function by influencing hormonal regulation and fertility. Aim of the review This review provides a detailed analysis of the toxicological aspects of nanoparticles, including cytotoxicity, oxidative stress, potential genotoxicity, and effects on immune responses such as inflammation and immunosuppression. In vivo biodistribution, organ accumulation, and effects on liver enzymes are also discussed, emphasizing the role of the liver in drug metabolism and the potential risk of impaired detoxification. Additionally, the review examines the effects of nanoparticles on the gut microbiome and reproductive system. It emphasizes their capacity to disrupt the microbial balance, the intestinal barrier integrity, and reproductive hormone homeostasis. We discuss regulatory issues for nanotechnology-based medicinal products, emphasizing the importance of standardized testing protocols and long-term safety assessments. Finally, future perspectives and developmental directions for nanoparticles have been highlighted. Conclusion This review highlights the need for a comprehensive understanding of nanoparticle toxicity mechanisms, which is crucial for their safe design and further development in nano-based therapy.