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，Davita L。密西西比大学的沃特金斯正在开发一种聚合物系统，这种系统可以封装生物相容的有机荧光团，用于荧光成像。 荧光团是含有称为π键的特殊碳-碳双键的染料。 当这些π键用特定波长的光照射时，它使荧光团能够重新发射该光，但具有不同的波长和更高的强度。 这种独特的特性使它们特别适用于生物成像应用。 在本研究中，将首先制备包含亲水性（亲水性）和亲油性（亲脂性）片段的生物相容性两亲聚合物。 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胶囊。 将使用几种光谱技术研究聚合物组装和封装过程中发生的各种动态过程。 与这项研究相关的结果有可能推动生物成像领域的发展，并进一步了解纳米限制环境中荧光团的光学性质。 这项工作是一项多学科的研究，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，并为功能性聚合物材料提供设计指南。 具体的推广工作将集中在转学生和/或具有非传统学术途径的学生的研究活动，因为他们构成了密西西比州大学生人口的重要组成部分。 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。 多样化的学术人口也将更多地接触到荧光成像的新兴和动态领域，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。 这项研究将开发新的方法，生物相容性的有机荧光团的荧光成像。 具体重点将放在开发具有第二近红外窗口（NIR-II，1000-1400 nm）光学特性的线性-树枝状嵌段共聚物和染料-聚合物共轭物上，由于当前试剂的稳定性和生物相容性较差，近年来已成为高度优先事项。 通过采用两亲性基板，自组装的基本机制，在定义良好，均匀的纳米结构的理想荧光成像的结果将得到阐明。 从大分子设计的角度出发，将由聚乳酸、聚己内酯等聚酯组成的疏水嵌段合成线形-树枝状嵌段共聚物。 亲水性树枝状分支将由聚酰胺胺组成。具有能够自组装成单分散胶束结构的聚集诱导发射分子框架的NIR-II荧光染料将被策略性地设计为具有噻吩并噻二唑和噻吩并硒二唑单元作为核心受体结构。 这项研究与有机和物理化学以及材料科学的原理相关。这项工作有可能通过提供对非常规相关生物物理现象的更深入理解来促进生物成像的发展。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。

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.