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

非技术性描述：许多疾病，如癌症，是可怕的，因为往往，他们被诊断晚时，治疗证明无效。此外，当治疗可用时，它涉及使人衰弱的副作用，包括其他危及生命的情况。因此，主要的医疗保健目标是早期、无创的准确诊断和有效的治疗干预，而不会产生有害的副作用。在这里，由来自两所大学的药物化学家和工程师领导的跨学科科学团队将开发和研究单一临床实施背后的基础科学，其双重目标是改进诊断超声成像和仅在目标区域有效的靶向治疗。该团队的目标是合成纳米尺寸的聚合物颗粒。它们在结构上与身体细胞相似，可以将治疗药物带到避开身体防御系统的目标区域。这些粒子经过化学工程处理，在只有在疾病条件下才能发现的特定化学环境中内爆，并运送它们的货物。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性质，以优化其预期效果及其超声反射率背后的机制。主要研究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。技术描述：本项目的目标是对聚合物纳米颗粒（聚合物囊泡）进行基础研究，这些聚合物纳米颗粒被编程为在疾病中常见的特定生化环境下释放其封装的内容物，同时对超声做出响应，以允许成像和超声辅助释放。它使用降低的氧分压作为模型触发释放。拟议的研究将开发多峰聚合物纳米颗粒的设计原则，用于未来肿瘤药物输送和同步超声成像的应用。该团队将优化聚合物设计，使所得聚合物囊泡对降低的氧气水平做出反应，并释放封装的内容物。纳米粒子将被制成捕获空气，允许在它们被破坏之前同时进行超声成像。这些回声内容轴承聚合物囊泡将在三维（3D）培养的癌细胞含有缺氧壁龛进行测试。该奖项将支持扩大代表性不足的少数民族参与研究和教育的活动。该奖项反映了NSF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。

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.