Controlled Amplification of Photochemical Reactions in Conjugated Polymer Nanoparticles

在这个由化学部化学结构、动态和机制B项目资助的项目中，威廉玛丽学院化学系的伊丽莎白J.哈布伦教授准备并研究了作为光化学（光诱导）反应放大器的纳米颗粒。例如，化疗药物可以附着在光反应性分子上，这种分子只在肿瘤部位释放药物，而不是在全身释放。光反应分子必须有效地反应，以使光的剂量最小化，但在暴露于正常的室内光时，它们的反应效率又不高。为了优化这一过程，Harbron教授的研究小组通过将荧光聚合物与光反应分子结合来合成光反应纳米颗粒。在这些新的纳米颗粒中，聚合物收集光能并将其传递给附着的光反应分子。目前的项目开发在小分子的光释放和活性氧的生产和检测中的应用。应用于光动力疗法和传感器的开发。该项目还为本科生和硕士生提供培训，在获得学术和职业规划建议的同时，学习有机化学、物理化学和分析化学技术。在实验室之外，Harbron教授继续担任化学女性导师网络和威廉和玛丽学者本科研究项目的导师，该项目旨在培养来自代表性不足群体的学生的研究技能。哈布伦教授在她的院系成立了一个新的多元化、外联和宣传委员会，并担任该委员会的主席，该委员会致力于扩大对科学的参与，促进校园内的科学对话。光是分子转化的一种有吸引力的刺激，因为它可以以高时空分辨率和曝光能量和强度控制传递到样品中。与光刺激相结合，光反应分子正被用于越来越多的令人兴奋的应用，从成像到催化。理想的光响应物质对光的反应是有效的，但对周围环境光的反应又不那么有效。在反应性方面实现这种平衡是该领域的主要挑战之一。其他挑战包括水溶性和调节可见光到近红外区域的光响应性。为了解决这些挑战，目前的项目将光响应染料与共轭聚合物纳米颗粒（cpn）配对。这些是非常明亮的荧光团，吸收和发射可见光到近红外线。它们可以悬浮在水中。当掺杂染料时，cpn充当强大的光收集器，通过荧光共振能量转移（FRET）将数百个发色团的能量汇集到单个染料分子中。将cpn的高效激发和能量转移过程与染料的低效率光化学反应配对，以受控的方式放大染料的反应活性。该项目优化了“可控放大”方法，并将其扩展到解决光反应性挑战。具体目标是：开发掺杂可光移保护基团的CPN以增强和控制光释放，并使用掺杂光致变色染料的CPN来量化CPN的性质，从而最大化光反应性。该研究还寻求开发既能产生超氧化物又能通过比例荧光报告其相对浓度的cpn。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。

In this project funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Elizabeth J. Harbron of the Department of Chemistry at the College of William and Mary prepares and studies nanoparticles which act as amplifiers for photochemical (light-induced) reactions. As one example, chemotherapy drugs can be attached to light-reactive (photoreactive) molecules which release their drug only at the site of the tumor instead of throughout the body. Photoreactive molecules must react efficiently so that the dose of light is minimized, but not so efficiently that they react when exposed to normal room light. In order to optimize this process, Professor Harbron's research group synthesizes photoreactive nanoparticles by combining fluorescent polymers with photoreactive molecules. In these new nanoparticles, the polymer gathers light energy and delivers it to the attached photoreactive molecules. The current project develops applications in the photorelease of small molecules and in the production and detection of reactive oxygen species. Applications are envisioned in photodynamic therapy and sensor development. This project also serves as training for undergraduate and master's level research students, who learn organic, physical, and analytical chemistry techniques while receiving academic and career planning advise. Outside of the lab, Professor Harbron continues to work as a mentor with the Chemistry Women Mentorship Network and with the William and Mary Scholars Undergraduate Research Program, which seeks to develop research skills in students from underrepresented groups. Professor Harbron founded and chairs a new Diversity, Outreach, and Publicity committee in her department that is working to broaden participation in science and promote scientific dialogue on campus. Light is an appealing stimulus for molecular transformations because it can be delivered to a sample with high spatiotemporal resolution and control of exposure energy and intensity. In conjunction with light stimulation, photoresponsive molecules are being used in an increasing number of exciting applications, from imaging to catalysis. The ideal photoresponsive substance reacts efficiently with light and yet not so efficiently that it responds to ambient light in an uncontrolled fashion. Achieving this balance in reactivity is one of the major challenges in the field. Other challenges include water solubility and tuning light responsiveness into the visible to near-infrared region. To address these challenges, the current project pairs photoresponsive dyes with conjugated polymer nanoparticles (CPNs). These are exceptionally bright fluorophores that absorb and emit in the visible to near-infrared. They can be suspended in water. When doped with dyes, CPNs act as powerful light harvesters, funneling the energy of hundreds of chromophores to a single dye molecule via fluorescence resonance energy transfer (FRET). Pairing the CPNs' efficient excitation and energy transfer processes with a dye's less efficient photochemical reaction amplifies the reactivity of the dye in a controlled fashion. This project optimizes the "controlled amplification" approach and extends it to address photoreactivity challenges. The specific aims are: to develop CPNs doped with photoremovable protecting groups to enhance and control photorelease, and to use CPNs doped with photochromic dyes to quantify the CPN properties that maximize photoreactivity. The research also seeks to develop CPNs that both generate superoxide and report on its relative concentration via ratiometric fluorescence.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.