A Study of Water-Spread Polymer Micelles on Water Surface: Toward Developing a First-in-Kind Polymer Lung Surfactant Therapy

美国每年约有20万患者被诊断为急性呼吸窘迫综合征（ARDS），原因包括病毒感染（例如COVID-19）、身体创伤和吸入化学物质。被诊断为急性呼吸窘迫综合征（严重低血氧水平）的患者面临着惊人的40%死亡率。用于治疗某些呼吸系统疾病的动物源性肺表面活性物质替代疗法在治疗ARDS方面尚未取得成功。因此，迫切需要一种有效的治疗方法，超越目前的治疗方法（机械通气）。研究人员的实验室正在开拓一种变革性的首创“聚合物肺表面活性剂（PLS）”疗法，该疗法由嵌段共聚物组成，可以解决传统动物源性肺表面活性剂疗法的局限性。通过研究它们的基本行为，可以在PLS的开发中取得进展，并希望最终将这项研究转化为改善人类健康结果。肺表面活性物质替代疗法是界面科学研究的重要成果之一。仅在美国，这项肺表面活性物质技术每年就拯救了3万多名内源性肺表面活性物质缺乏的新生儿。当肺实质损伤导致天然肺表面活性物质功能受损时，成人也会出现类似的症状。不幸的是，用于治疗肺表面活性物质储存不足的新生儿的表面活性物质替代疗法尚未显示对ARDS有效。合成的两亲嵌段共聚物聚（苯乙烯）-聚（乙二醇）（PS-PEG）胶束在ARDS的治疗中有很大的应用前景。为了进一步发展该技术，需要对水扩散嵌段共聚物的界面力学和输运行为的基础科学有更深入的了解。这就是这个奖项旨在填补的空白。具体来说，实验提供了对水扩散PS-PEG胶束在水面上独特表面力学行为的分子起源的理解（进一步优化PLS配方）。将研究水扩散PS-PEG胶束的表面流变行为（以了解其独特的蛋白质抗性行为）。将研究通过肺气道的聚乙二醇胶束溶液的界面流动和涂层特性（这将有助于优化聚乙二醇的输送过程）。该奖项为研究生和本科生提供多学科培训，以学习界面工程中最先进的概念和技能。可利用的校园资源，为本计划增加招募代表性不足/少数族裔本科生。为当地高中生提供研究体验机会。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Every year around 200,000 patients in the US are diagnosed with Acute Respiratory Distress Syndrome (ARDS) as a result of such causes as viral infection (e.g., COVID-19), physical trauma, and inhalation of chemicals. Patients diagnosed with ARDS (critically low blood oxygenation levels) face a staggering 40% mortality rate. The use of animal-derived lung surfactant replacement therapy that has been used to treat certain respiratory conditions has not been successful in treating ARDS. Therefore, there is dire need for an effective therapeutic that goes beyond current treatments (mechanical ventilation). The investigator’s laboratory is pioneering a transformative first-in-kind “Polymer Lung Surfactant (PLS)” therapy that is composed of a block copolymer and can address limitations of conventional animal-derived lung surfactant therapeutics. By studying their fundamental behavior, advances can be made in the development of a PLS with the hope of ultimately translating this research to improvements in human health outcomes.Lung surfactant replacement therapy is one of the greatest achievements in interfacial science research. Each year in the US alone, this lung surfactant technology saves over 30,000 newborns suffering from deficiency of endogenous lung surfactant. Adults can suffer from similar symptoms (ARDS) when the function of their native lung surfactant becomes impaired due to injury to lung parenchyma. Unfortunately, the surfactant replacement therapy which is used to treat neonates with insufficient lung surfactant stores has not been shown to be effective for ARDS. It has been discovered that micelles derived from a synthetic amphiphilic block copolymer, poly(styrene)-poly(ethylene glycol) (PS-PEG), show great promise for the treatment of ARDS. A greater understanding of the fundamental science of the interfacial mechanical and transport behavior of water-spread block copolymers is required for further advancement of this technology. This is the gap that this award aims to fill. Specifically, the experiments provide understanding on the molecular origin of the unique surface mechanical behavior of water-spread PS-PEG micelles on water surface (toward further optimization of PLS formulations). Surface rheological behavior of water-spread PS-PEG micelles (to understand their unique protein resistant behavior) will be studied. Interfacial flow and coating properties of PS-PEG micelle solutions through lung airways (which will help optimize PLS delivery processes) will be investigated. This award provides multidisciplinary training for graduate and undergraduate students involved to learn state-of-the-art concepts and skills in interfacial engineering. Available campus resources are used to enhance recruitment of underrepresented/minority undergraduate students for this project. Local high school students are provided with research experience opportunities.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.