Surface Free Energy of Nanoparticles Regulates the Formation of Pulmonary Surfactant Biomolecular Corona

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Understanding the complex behavior and interaction between extremely tiny particles (nanoparticles) and living organisms is of crucial importance in advancing the science of drug delivery, as well as proactively preventing the environmental, health and safety ramifications after inhalation of noxious gases and/or infectious airborne particles. Once inhaled, nanoparticles immediately adsorb biological molecules normally found in the surface lining of the lung, enveloping the nanoparticle with a unique biomolecular corona that defines its subsequent cellular interactions. To date, little is known about the biological and physicochemical driving forces regulating the formation of the biomolecular corona. It is also unknown what potential deleterious effects may result from the interactions of these corona-covered particles on the human lung. Thus, the goal of this research project is to develop novel experimental methods for understanding the thermodynamic driving forces responsible for the formation of the biomolecular corona of inhaled nanoparticles. Understanding the dynamics of these pulmonary/nanoparticle interactions will provide novel insights into the mechanism of pulmonary toxicity of inhaled nanoparticles. By collaborating with local healthcare providers, the overarching goal is to apply the knowledge gained from this research to elucidate the environmental risks of a library of nanoparticles, particularly those that are likely to adversely affect the lungs of infants and children. Through the unique location of the University of Hawaii, the investigator is dedicated to promoting participation in this research with Native Hawaiians, Pacific Islanders, and students from underrepresented minority groups.The objective of this research project is to test a novel hypothesis that the surface free energy of nanoparticles regulates the structure and chemical composition of the pulmonary surfactant biomolecular corona, using a combined experimental and computational approach. Although it is well known that the hydrophobicity of nanoparticles plays a critical role in defining the structure and chemical configuration of the biomolecular corona, the biomolecular events have never been elucidated or systematically studied. This is largely due to the lack of quantitative methods for characterizing the hydrophobicity of nanoparticles. The PI will fill this gap by developing a novel optical method for determining the surface free energy of nanoparticles as a quantitative measure of its hydrophobicity. This method relies on an innovative measuring principle of manipulating the intermolecular forces between nanoparticles across liquid media. The methodology is both unique and innovative, and distinctly different from existing methods. Once developed and validated, it has the potential to offer a standard, low-cost, and easy-to-use method for quantitatively characterizing the surface free energy and hydrophobicity of particulate matter. The PI will experimentally study particle-size dependent surface free energy, and the energetic effect of the biomolecular corona utilizing a library of pristine nanoparticles. Knowledge from this study will provide insight into the thermodynamic driving forces at play in the formation of the biomolecular corona. This research will also advance the current understanding of the nano-bio interaction in the lungs and bridge the gap between the available biophysicochemical data and nanotoxicological data. Broader implications include a translational research methodology and approach in designing nanoparticle-based pulmonary drug delivery systems and in furthering an understanding of the pathophysiology of respiratory injury caused by noxious air pollutants and other environmental respiratory hazards. Ultimately, the developed technology offers the potential for widespread usage in many platforms, both in the laboratory and in studies performed on humans to improve respiratory health. The PI is actively engaged in the Native Hawaiian Science & Engineering Mentorship Program (NHSEMP) and the Society of Women Engineers (SWE) at the University of Hawaii. The PI will support one graduate student and several undergraduate students from traditionally underrepresented groups.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.