Скачать или смотреть Structure activity relationships in nanotoxicology

Nanolecture event sponsored by the HSPH-NIEHS Nanosafety Center, hosted October 10, 2019 at Harvard TH Chan School of Public Health

Abstract: Using a predictive toxicological approach with the focus on elucidating nano-bio interactions at nano-bio interface, we have screened over 100 ENMs of major types of engineered nanomaterials (ENMs) and developed important structure activity relationships (SAR) that can be used for developing adverse outcome pathways (AOPs) in predicting in vivo injury outcomes. Among these SARs, we found that ENMs including rare earth oxides (REOs), graphene and graphene oxides (GO), fumed silica, as well as high aspect ratio materials (such as CNTs and CeO2 nanowires etc.) could trigger the NLRP3 inflammasome activation and IL-1β production in macrophages and subsequent series of events including production of pro-fibrogenic cytokines including TGF-β1 and PDGF-AA in vitro and in vivo, resulting in synergistically cell-cell communication among macrophages, epithelial cells, and fibroblasts in a process called epithelial-mesenchymal transition (EMT) and collagen deposition in the lung as the adverse outcomes. Intriguingly, different ENMs engage a range of distinct pathways leading to the NLRP3 inflammasome activation and IL-1β production in macrophages, which include frustrated phagocytosis, physical piercing, plasma membrane perturbation or damage to lysosomes due to high aspect ratio, surface functional groups, surface reactivity, dissolution and transformation. In this nanolecture, I will introduce in detail some of these major SARs leading to chronic lung effects and how this information could be used for safer design of nanomaterials for their applications.


Biographical Sketch: Dr. Tian Xia is the Associate Professor of Medicine in Division of NanoMedicine, Department of Medicine at University of California, Los Angeles (UCLA). His main research area is on the environmental and health impacts of engineered nanomaterials with the goal to understand the nanostructure property activity relationships. Predictive toxicology and high throughput screening are the main approaches for his research. His has established toxicological profiles for over 100 different nanomaterials covering the major material categories including carbonaceous materials (fullerene, graphene, graphene oxide, carbon nanotubes (single-, multi-walled)), metal (Au, Ag) and metal oxides (transition metal oxide, rare earth oxide), silica, III-V materials. Research findings have been used for safer design of nanomaterials and development of environmental and biomedical applications. He has published over 130 articles and he was named Highly Cited Researcher in Chemistry in 2016 and 2018 by Clarivate Analytics, with total citation over 30,000 and H factor at 60 according to Google Scholar.