#1604119 The rapid development of nanotechnology and a widespread proliferation of nano-enabled consumer products post an increasing concern of the potential adverse environment, health, and safety (EHS) impacts of nanoparticles (NPs), which feature a characteristic size less than 100 nm. Most NPs are lightweight and respirable. Once inhaled, NPs can penetrate into the lungs and interfere with the respiratory function. The entire surface of the lungs is lined with a lipid-protein pulmonary surfactant (PS) film which serves an important physiological function of host defense and surface tension reduction. Interactions between inhaled NPs and the PS film hence represent the initial nano-bio phenomena in the lungs. Such interactions determine the fate of the inhaled NPs and their potential therapeutic or toxicological effects. This proposal will investigate the detailed mechanism of NP-PS interactions using novel experimental and computational techniques developed in the PI's laboratory. These techniques allow high-fidelity simulations of air pollution scenarios in which NPs are inhaled and deposited at the surface of the PS film. Using these model systems, potential environmental hazards of NPs and nano-enabled products, such as NP-containing sprays and paints, will be thoroughly evaluated. The PI will specifically focus on studying the potential risk of respirable NPs for infants and children whose fragile respiratory system makes them more vulnerable to NP exposure than adults. The proposed study will help provide a useful metric for regulating and overseeing commercial applications of nanotechnology towards a safer and sustainable development.
The research goal of this proposal is to study the detailed biophysicochemical mechanisms by which airborne engineered nanoparticles (NPs) interact with natural pulmonary surfactant (PS). This research is highly novel due to the following two main perspectives. First, NP-PS interactions will be studied using a combined approach of multiscale in vitro and in silico simulations. The in vitro study relies on biophysical simulations using a novel experimental methodology recently developed in the PI's laboratory. With this in vitro model, nano-bio interactions at the PS film will be mimicked with fully controlled NP aerosol dosimetry and under physiologically relevant respiratory conditions. The in silico study relies on high-fidelity molecular dynamics simulations which allow probing the detailed molecular mechanism of NP translocation across the PS film. Second, the PI will carry out the first comprehensive study of the biomolecular corona bound to NPs in contact with lung fluids, i.e., the so-called PS biomolecular corona. With correlated high-precision mass spectrometry and molecular dynamics simulations, the proposed project will reveal the biochemical composition and biophysical conformation of the PS biomolecular corona with unprecedented details. This research is expected to significantly advance current understanding of nano-bio interactions in the respiratory system and to provide novel insight into the EHS impacts of nanotechnology.
The broader impacts of this proposal are rich and multifarious. In vitro and in silico simulations developed in this proposal are cost-effective means of exploring the EHS impacts of nanotechnology. The proposed study will complement the current nanotoxicological knowledge obtained from cell culture and animal-models. The biophysicochemical mechanism revealed by this study has clear transformative values for designing NP-based pulmonary drug delivery and for better understanding the pathophysiology of respiratory diseases related to air pollution and particle insult. In collaboration with local healthcare providers, the PI is engaged in activities of increasing the public awareness of the potential risk of respirable NPs for infants and children. Given the unique location of the University of Hawaii, the PI is dedicated to promoting participation of Native Hawaiians, Pacific Islanders, and students from other underrepresented groups and low-income families. The PI will also develop undergraduate and graduate engineering curricula with interdisciplinary components, and help enhance the infrastructure for research and education.
