The Evolution of Nanoparticle Regulation: A Meta-Analysis of Research Trends and Historical Parallels (2015-2025)

Objective: We analyzed nanoparticle regulation research to examine the evolution of regulatory frameworks, identify major thematic structures, and evaluate current challenges in the governance of rapidly advancing nanotechnologies. By drawing parallels with the historical development of radiation regulation, the study aimed to contextualize emerging regulatory strategies and derive lessons for future governance. Methods: A total of 9095 PubMed-indexed articles published between January 2015 and October 2025 were analyzed using text mining, keyword frequency analysis, and topic modeling. Preprocessed titles and abstracts were transformed into a TF-IDF (Term Frequency-Inverse Document Frequency) document-term matrix, and NMF (Non-negative Matrix Factorization) was applied to extract semantically coherent topics. Candidate topic numbers (K = 1-12) were evaluated using UMass coherence scores and qualitative interpretability criteria to determine the optimal topic structure. Results: Six major research topics were identified, spanning energy and sensor applications, metal oxide toxicity, antibacterial silver nanoparticles, cancer nano-therapy, and nanoparticle-enabled drug and mRNA delivery. Publication output increased markedly after 2019 with interdisciplinary journals driving much of the growth. Regulatory considerations were increasingly embedded within experimental and biomedical research, particularly in safety assessment and environmental impact analyses. Conclusions: Nanoparticle regulation matured into a dynamic multidisciplinary field. Regulatory efforts should prioritize adaptive, data-informed, and internationally harmonized frameworks that support innovation while ensuring human and environmental safety. These findings provide a data-driven overview of how regulatory thinking was evolved alongside scientific development and highlight areas where future governance efforts were most urgently needed.