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

了解极其微小的颗粒（纳米颗粒）和生物体之间的复杂行为和相互作用对于推进药物输送科学以及积极预防吸入有毒气体和/或传染性空气传播颗粒后的环境，健康和安全后果至关重要。一旦被吸入，纳米颗粒立即吸附通常在肺的表面衬里中发现的生物分子，用独特的生物分子冠包围纳米颗粒，该生物分子冠限定其随后的细胞相互作用。到目前为止，很少有人知道的生物和物理化学的驱动力调节生物分子冠的形成。也不知道这些电晕覆盖的颗粒对人肺的相互作用可能导致什么潜在的有害影响。因此，本研究项目的目标是开发新的实验方法，以了解负责形成吸入纳米颗粒的生物分子冠的热力学驱动力。了解这些肺/纳米颗粒相互作用的动力学将为吸入纳米颗粒的肺毒性机制提供新的见解。通过与当地医疗保健提供者合作，总体目标是应用从这项研究中获得的知识来阐明纳米颗粒库的环境风险，特别是那些可能对婴儿和儿童肺部产生不利影响的纳米颗粒。通过夏威夷大学独特的地理位置，研究者致力于促进夏威夷土著人，太平洋岛民和来自代表性不足的少数群体的学生参与这项研究。这项研究项目的目的是测试一个新的假设，即纳米颗粒的表面自由能调节肺表面活性剂生物分子冠的结构和化学组成，结合实验和计算方法。尽管众所周知，纳米颗粒的疏水性在定义生物分子冠的结构和化学构型中起着关键作用，但生物分子事件从未被阐明或系统地研究。这在很大程度上是由于缺乏表征纳米颗粒疏水性的定量方法。PI将通过开发一种新的光学方法来确定纳米颗粒的表面自由能作为其疏水性的定量测量来填补这一空白。这种方法依赖于一种创新的测量原理，即操纵液体介质中纳米颗粒之间的分子间力。该方法既独特又创新，与现有方法截然不同。一旦开发和验证，它有可能提供一个标准的，低成本的，易于使用的方法，用于定量表征颗粒物的表面自由能和疏水性。PI将通过实验研究颗粒大小相关的表面自由能，以及利用原始纳米颗粒库的生物分子电晕的能量效应。从这项研究的知识将提供深入了解热力学驱动力在发挥生物分子冠的形成。这项研究还将推进目前对肺部纳米生物相互作用的理解，并弥合现有生物化学数据和纳米毒理学数据之间的差距。更广泛的影响包括一个转化的研究方法和方法，在设计纳米颗粒为基础的肺部给药系统，并在进一步了解呼吸损伤的病理生理学引起的有毒空气污染物和其他环境呼吸危害。最终，开发的技术提供了在许多平台上广泛使用的潜力，无论是在实验室还是在对人类进行的改善呼吸健康的研究中。 PI积极参与夏威夷土著科学工程导师计划（NHSEMP）和夏威夷大学的女工程师协会（SWE）。PI将支持一名研究生和几名本科生，他们来自传统上代表性不足的群体。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.