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

水面上水铺展聚合物胶束的研究：开发首创聚合物肺表面活性剂疗法

• 批准号: 2211843
• 负责人: You-Yeon Won
• 金额: $ 40.34万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2211843&HistoricalAwards=false
• 关键词: Study; Water; Spread; Polymer; Micelles

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.

美国每年约有 200,000 名患者因病毒感染（例如 COVID-19）、身体创伤和吸入化学物质等原因被诊断为急性呼吸窘迫综合征 (ARDS)（诊断为 ARDS 的患者数量极低）。血氧水平）面临高达 40% 的死亡率。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尚未成功治疗 ARDS。因此，迫切需要一种超越现有治疗方法（机械通气）的有效治疗方法。研究人员的实验室正在开创一种革命性的首创“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，通过研究其基本行为，可以在 PLS 的开发方面取得进展，并希望最终将这项研究转化为改善人类健康结果。替代疗法是界面科学研究中最伟大的成就之一，仅在美国，这种肺表面活性剂技术就可以挽救超过 30,000 名患有内源性肺表面活性剂缺乏症的新生儿。不幸的是，用于治疗肺表面活性剂储存不足的新生儿的表面活性剂替代疗法尚未被证明对 ARDS 有效。研究发现，源自合成两亲性嵌段共聚物聚苯乙烯-聚乙二醇 (PS-PEG) 的胶束在治疗 ARDS 方面显示出巨大的前景。该奖项旨在填补水铺展嵌段共聚物的分子起源和传输行为这一空白。将研究水铺展的 PS-PEG 胶束在水表面的表面流变行为（以了解其独特的蛋白质抗性行为）。将研究通过肺气道的 PS -PEG 胶束解决方案（这将有助于优化 PLS 输送过程）。该奖项为参与学习界面工程领域最先进概念和技能的研究生和本科生提供多学科培训。可用的校园资源用于加强该项目招募代表性不足/少数族裔本科生，为当地高中生提供研究经验机会。该奖项是 NSF 的法定使命，并通过使用基金会的智力优势和更广泛的评估被认为值得支持。影响审查标准。

项目成果

Nanotechnology‐enhanced radiotherapy and the abscopal effect: Current status and challenges of nanomaterial‐based radio‐immunotherapy

纳米技术增强放射治疗和远隔效应：基于纳米材料的放射免疫治疗的现状和挑战

• DOI: 10.1002/wnan.1924
• 发表时间: 2023-08
• 期刊: WIREs Nanomedicine and Nanobiotechnology
• 作者: Viswanath, Dhushyanth;Park, Jeehun;Misra, Rahul;Pizzuti, Vincenzo J.;Shin, Sung‐Ho;Doh, Junsang;Won, You‐Yeon
• 通讯作者: Won, You‐Yeon

Radiation-induced photodynamic therapy using calcium tungstate nanoparticles and 5-aminolevulinic acid prodrug

使用钨酸钙纳米颗粒和 5-氨基乙酰丙酸前药的放射诱导光动力疗法

• DOI: 10.1039/d3bm00921a
• 发表时间: 2023-01
• 期刊: Biomaterials Science
• 影响因子: 6.6
• 作者: Viswanath, Dhushyanth;Shin, Sung;Yoo, Jin;Torregrosa;Harper, Haley A.;Cervantes, Heidi E.;Elzey, Bennett D.;Won, You
• 通讯作者: Won, You

Polymer Lung Surfactants Attenuate Direct Lung Injury in Mice

聚合物肺表面活性剂减轻小鼠直接肺损伤

• DOI: 10.1021/acsbiomaterials.3c00061
• 发表时间: 2023-05
• 期刊: ACS Biomaterials Science & Engineering
• 影响因子: 5.8
• 作者: Fesenmeier, Daniel J.;Suresh, Madathilparambil V.;Kim, Seyoung;Park, Sungwan;Raghavendran, Krishnan;Won, You
• 通讯作者: Won, You

Surface Pressure-Area Mechanics of Water-Spread Block Copolymer Micelle Monolayers at the Air-Water Interface: Effect of Hydrophobic Block Chemistry

空气-水界面处水铺展嵌段共聚物胶束单层的表面压力面积力学：疏水嵌段化学的影响

• 发表时间: 2023-01
• 期刊: Langmuir
• 影响因子: 3.9
• 作者: Kim, Seyoung;Park, Sungwan;Fesenmeier, Daniel J.;Jun, Taesuk;Sarkar, Kaustabh;Won, You
• 通讯作者: Won, You

Determination of Glass Transition Temperatures in Bulk and Micellar Nanoconfined Polymers Using Fluorescent Molecular Rotors as Probes for Changes in Free Volume

使用荧光分子转子作为自由体积变化的探针测定块状和胶束纳米限制聚合物中的玻璃化转变温度

• DOI: 10.1021/acs.macromol.3c00968
• 发表时间: 2023-08-01
• 期刊: Macromolecules
• 影响因子: 5.5
• 作者: Seyoung Kim;Minhwan Lee;Hyun Chang Kim;YongJoo Kim;Won Bo Lee;You
• 通讯作者: You