Nanotoxicity/Nanobiointeraction: Challenges, Research Gaps, and Progress Beyond Traditional Toxicology
Saber M. Hussain, PhD, ATS Fellow
Previous publications have established a strong foundation for the acute, size-dependent toxicity of silver Nanomaterials (Ag NM), and identify oxidative stress as the mechanism of toxicity in a wide range of cell types. However there is a lack of knowledge, pertaining to realistic exposure doses, appropriate dosimetry, deposition efficiency, and long-term cellular consequences, based on nanomaterials (NM) physical parameters. To address these research gaps, we have developed a NM quick-screen procedure, using a multi-cell model approach, as well as low level acute and chronic NM studies to elucidate the subsequent impact on cell signaling and gene expression. Our acute, low-level Ag NM studies demonstrated that in the absence toxicity, the cells had significant alterations in cell signaling, gene expression, and inflammation; signifying an acute stress response. Furthermore, in these acute, low-level studies; the size, shape, and coating of the NM contributed to the observed cellular responses. In comparison, the low-level Ag NM chronic studies demonstrated increased activation of a p38 stress mediated pathway, which led to actin disorganization, increased cellular repair and heightened EGF signaling. The differences were significant in the observed response between acutely-dosed and chronically-dosed cells, indicating that studies evaluating the length of exposure to NMs are imperative. Taken together, these studies indicate the need to progress beyond traditional toxicity evaluations to fully understand the implications of NM exposure, with emphasis on the physical and chemical behavior of particles in a cell environment.
Saber Hussain, Ph.D., ATS Fellow
Senior Scientist- Nanobiotechnology Group Lead
Molecular Bioeffects Branch,Human Effectiveness Directorate
711 Human Performance Wing
Air Force Research Laboratory (711 HPW/RHDJ)
Wright State University School of Medicine, Pharmacology/Toxicology,
Saber Hussain, Senior Scientist and Nanotoxicology Group Lead, Molecular Bioeffects Division, Wright-Patterson Air Force Base, Ohio. Dr. Hussain began (1987) his scientific career as a toxicology research fellow at the highly regarded Indian Institute of Chemical Technology (IICT) and received his doctorate degree in 1991. Here, his novel exploration of heavy metal biotransfer between different proteins in complex biological environment led to a series of prestigious research fellowships in Italy, Switzerland, and the U.S. Dr. Hussain joined the Air Force Research Laboratory at Wright-Patterson AFB in 1999, where his research interests transitioned into evaluating potential toxicity arising from the physicochemical properties of nanoscale structures. His research addressing nanomaterial toxicity and its associated environmental/occupational safety and health risks has resulted in author/co-authorship of 100 peer-reviewed publications, 9 book chapters, and 200 technical abstracts.
He is full affiliated Associate Professor at the Pharmacology and Toxicology Department, Wright State University School of Medicine. He is currently an Associate Editor of Toxicological Sciences and serves as an editorial member of several other toxicology journals. He is a Fellow of the Academy of Toxicological Sciences and US Air Force Research Laboratory. He serves as an expert reviewer for several government and private organizations. Dr. Hussain has been the recipient of numerous scientific awards including AstraZeneca Lectureship award and has established a strong collaborative network with over 25 organizations of national and international repute.