Exploring the interactions between nanoparticles and biological organisms using advanced imaging and omics...

Nanoparticles have been a focus of drug delivery research for nearly three decades, yet their extremely low clinical translation rates and mediocre clinical performance fail to justify the substantial investment. The unclear in vivo fate of nanoparticles remains a significant obstacle to further enhancing their application potential. Therefore, it is crucial to evaluate the in vivo fate of nanoparticles with high spatial resolution, high temporal resolution, and high sensitivity through advanced tracking technologies. Meanwhile, as various omics technologies have been employed to characterize molecular features in both normal and pathological states of organisms, they are also increasingly applied to analyze interactions between nanoparticles and biological systems. However, technical limitations and interdisciplinary challenges have confined much research to examining the distribution characteristics of nanoparticles and the secondary responses they mediate in organisms, while leaving the bio-disposition of nanoparticles within organisms poorly understood-a scenario regarded as an incomplete picture of nanoparticle-organism interactions. This review will summarize recent advances in nanoparticle imaging technologies and omics approaches. It then synthesizes and discusses research paradigms investigating interactions between nanocarriers and biological systems through multi-omics studies. In particular, the application of multi-omics in nanoparticle optimization, target discovery, the characterization of the nanoparticle bio-disposition will also be examined. STATEMENT OF SIGNIFICANCE: (1) The novelty and significance of the work with respect to the existing literature. In this review, we conclude the applicability of omics technologies in three aspects: the mechanism of action, pharmacodynamic performance, and toxicological performance of nanoparticles. Meanwhile, this review outlines how omics technologies can be leveraged to investigate the in vivo processing of nanoparticles. In short, this review describes how to study the in vivo fate of nanoparticles through the fresh perspective of omics. (2) The scientific impact. Omics technologies have been widely applied in pathology and physiology. We believe omics approaches can also complement traditional imaging techniques, thereby advancing the development of more controllable and effective nanoparticles and biomaterials.