Collaborative Research: Design and mechanistic studies on microenvironment-sensitive polymeric nanoparticles for simultaneous contents release and ultrasound imaging

合作研究：微环境敏感聚合物纳米粒子的设计和机理研究，用于同时释放内容物和超声成像

• 批准号: 2322963
• 负责人: Sanku Mallik
• 金额: $ 29.83万
• 依托单位: North Dakota State University Fargo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2322963&HistoricalAwards=false
• 关键词: Collaborative; Research; Design; mechanistic; studies

Non-technical Description:Many diseases, such as cancer, are dreadful because often, they are diagnosed late when therapy proves ineffective. Moreover, when therapy is available, it involves debilitating side effects, including other life-threatening conditions. The primary healthcare objectives, therefore, are early, noninvasive accurate diagnosis and effective therapeutic intervention without harmful side effects. Here a cross-disciplinary scientific team led by a pharmaceutical chemist and an engineer from two universities will develop and study the fundamental science behind a single clinical implement with the dual aim of improved diagnostic ultrasound imaging and targeted therapy which becomes active only in the target region. The team aims at synthesizing nanometer-size polymeric particles. They are similar in structure to body cells and can carry therapeutics to target areas evading the body’s defense system. The particles are chemically engineered to implode in a specific chemical environment found only in diseased conditions and deliver their cargo. The proposed research will systematically investigate the chemistry of these nanoparticles through experiments and theory to optimize their desired effects and the mechanism behind their ultrasound reflectivity. The principal investigators have proposed an array of educational activities involving high school interns, undergraduates, and Ph.D. students in multi-disciplinary projects with real-life clinical applications preparing them to enter the twenty-first-century workforce.Technical Description:The objective of this proposal is to conduct foundational studies on polymer nanoparticles (polymersomes) that are programmed to release their encapsulated contents under specific biochemical environments common in diseases and simultaneously are responsive to ultrasound to allow imaging and ultrasound-assisted release. It uses reduced oxygen partial pressure as a model trigger for release. The proposed studies will develop the design principles of multimodal polymer nanoparticles for future applications in drug delivery to tumors and simultaneous ultrasound imaging. The team will optimize polymer design so that the resultant polymersomes become responsive to the reduced oxygen levels and release the encapsulated contents. The nanoparticles will be made to entrap air allowing simultaneous ultrasound imaging before their destruction. These echogenic content-bearing polymersomes will be tested in three-dimensional (3D) cultures of cancer cells containing hypoxic niches. The award will support activities that broaden participation of underrepresented minorities in research and education.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.

非技术描述：许多疾病，例如癌症，令人恐惧，因为经常在治疗证明无效时被诊断出来。此外，当可以进行治疗时，它涉及使副作用使人衰弱，包括其他威胁生命的疾病。因此，主要的医疗保健目标是早期的，无创的准确诊断和有效的治疗干预措施，而没有有害的副作用。在这里，由药物化学家和两所大学的工程师领导的跨学科科学团队将开发和研究单个临床实施背后的基本科学，其双重目的是改进诊断超声成像和靶向治疗，仅在目标区域中活跃起来。该团队旨在合成纳米大小的聚合物颗粒。它们的结构与人体细胞相似，并且可以对逃避人体防御系统的目标区域进行治疗。这些颗粒是在仅在脱离条件下发现并运送货物的特定化学环境中进行化学设计的。拟议的研究将通过实验和理论系统地研究这些纳米颗粒的化学，以优化其所需的效果以及其超声反射率背后的机制。首席调查人员提出了一系列教育活动，涉及高中实习生，本科生和博士学位。 students in multi-disciplinary projects with real-life clinical applications preparing them to enter the twenty-first-century workforce.Technical Description:The objective of this proposal is to conduct foundational studies on polymer nanoparticles (polymeromes) that are programmed to release their encapsulated contents under specific biochemical environments common in diseases and simply are responsive to ultrasound to allow imaging and ultrasound-assisted release.它使用降低的氧部分压力，因为拟议的研究将开发多模式聚合物纳米颗粒的设计原理，以便将来在药物递送到肿瘤和简单的超声成像中应用。该团队将优化聚合物设计，以使所得的聚合物组对降低的氧气水平有反应并释放包封的含量。纳米颗粒将被制成诱捕空气，以使其在破坏之前进行简单的超声成像。具有回声含量的聚合物组将在含有低氧壁ches的癌细胞的三维（3D）培养物中进行测试。该奖项将支持扩大代表性不足少数群体研究和教育的活动的活动。该奖项反映了NSF的法定使命，并使用基金会的知识分子优点和更广泛的影响标准，被视为通过评估来获得宝贵的支持。