Harnessing the Aggregation Behavior of Near-Infrared (NIR-II) Fluorophores via Supramolecular Nano-scaffolds

在化学系大分子、超分子和纳米化学项目的支持下，密西西比大学的Davita L. Watkins正在开发聚合物系统，该系统可以封装生物相容性有机荧光团，用于荧光成像。荧光团是一种含有特殊碳碳双键的染料，叫做pi键。当这些键被特定波长的光照射时，它使荧光团重新发射出不同波长和更高强度的光。这种独特的特性使它们在生物成像应用中特别有用。在本研究中，将首先制备同时包含亲水（亲水）和亲油（亲脂）片段的生物相容性两亲性聚合物。它们的两亲性类似于其他人造化合物，如肥皂和洗涤剂，甚至是天然存在的脂蛋白。然后将合成的聚合物组装成能够捕获荧光团的定义明确的纳米级胶囊。各种动态过程将发生在聚合物组装和封装将研究使用几种光谱技术。与这项研究相关的结果有可能推动生物成像领域的发展，并进一步了解纳米受限环境中荧光团的光学特性。这项工作是一项多学科研究，其中发展的基本方面将为早期职业科学家的培训提供肥沃的土壤，并为功能聚合物材料的设计提供指导。具体的拓展工作将集中在转学生和/或非传统学术路径的学生的研究活动上，因为他们占密西西比州大学人口的很大一部分。这项研究将使下一代科学家具备解决复杂社会问题的技能、协作精神和创造力。多元化的学术群体也将更多地接触到荧光成像这一新兴的、充满活力的领域，使他们为不断扩大的STEM（科学、技术、工程和数学）劳动力做出贡献。本研究将开发用于荧光成像的生物相容性有机荧光团的新方法。重点将放在具有第二近红外窗口（NIR-II, 1000-1400 nm）光学性能的线性-树突嵌段共聚物和染料-聚合物共轭物的开发上，这是近年来由于现有试剂稳定性和生物相容性较差而成为优先考虑的问题。通过采用两亲性底物，自组装的基本机制，导致良好定义，均匀的纳米结构理想的荧光成像将被阐明。从大分子设计的角度来看，线性-树枝状嵌段共聚物将由聚乳酸和聚己内酯等聚酯组成的疏水嵌段合成。亲水的树枝状分支将由聚酰胺胺组成。本文将以噻吩噻二唑和噻吩硒二唑为核心受体结构，设计具有聚集诱导发光分子框架的NIR-II荧光染料，使其具有自组装成单分散胶束结构的能力。这项研究是与有机化学和物理化学原理以及材料科学相关的交叉领域。这项工作通过提供对非常规相关光物理现象的更深入理解，有可能为生物成像的发展做出贡献。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。

With the support of the Macromolecular, Supramolecular and Nanochemistry program in the Division of Chemistry, Davita L. Watkins of the University of Mississippi is developing polymeric systems that can encapsulate biocompatible organic fluorophores for fluorescence imaging. Fluorophores are dyes that contain special carbon-carbon double bonds called pi-bonds. When these pi-bonds are irradiated with light of a certain wavelength, it enables the fluorophores to re-emit that light but with a different wavelength and much higher intensity. This unique characteristic makes them particularly useful for bioimaging applications. In this research, biocompatible amphiphilic polymers containing both water-loving (hydrophilic) and oil-loving (lipophilic) segments will first be prepared. Their amphiphilic properties resemble those of other artificial compounds such as soaps and detergents, or even naturally occurring lipoproteins. Synthesized polymers will then be assembled to create well-defined nanosized capsules which are capable to trap fluorophores. Various dynamic processes that will occur during polymer assembly and encapsulation will be studied using several spectroscopic techniques. Results associated with this research have the potential to advance the field of bioimaging and further understanding of optical properties of fluorophores in nanoconfined environments. This work is a multi-disciplinary study in which fundamental aspects of development will provide fertile ground for the training of early career scientists and offer design guidelines toward functional polymeric materials. Specific outreach endeavors will focus on research activities for transfer students and/or students having nontraditional academic paths as they make up a significant portion of the collegiate population in the state of Mississippi. The research will equip the next generation of scientists with the skills, collaborative spirit, and creativity to solve complex societal problems. A diverse scholastic population will also become more exposed to the emerging and dynamic area of fluorescence imaging, preparing them to contribute to an expanding STEM (science, technology, engineering and mathematics) workforce. This research will develop new approaches to biocompatible organic fluorophores for fluorescence imaging. Specific emphasis will be placed on developing linear-dendritic block copolymers and dye-polymer conjugates with optical properties in the second near-infrared window (NIR-II, 1000–1400 nm), which has emerged as a high-priority in recent years due to poor stability and biocompatibility of current agents. By employing amphiphilic substrates, the fundamental mechanism of self-assembly that results in well-defined, uniform nanostructures ideal for fluorescence imaging will be elucidated. From the point of view of macromolecular design, linear-dendritic block copolymers will be synthesized with hydrophobic blocks consisting of polyesters such as polylactides and polycaprolactones. Hydrophilic dendritic branches will be composed of polyamidoamines. NIR-II fluorescent dyes with aggregation-induced emissive molecular frameworks capable of self-assembling into monodisperse micellar structures will be strategically designed with thienothiadiazole and thienoselenadiazole units as the core acceptor structures. This research is cross-cutting with relevance to principles of organic and physical chemistry, and materials science. The work has the potential to contribute to bio-imaging development by providing a deeper understanding of unconventional related photophysical phenomena.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.