Responsive Iron MRI probes with Enhanced Relaxivity

在化学结构，动力学和机理- b （CSDM-B）项目和化学部门化学测量和成像（CMI）项目的支持下，纽约州立大学布法罗大学化学系的Janet Morrow教授和她的团队正在开发基于铁配位配合物的新型磁共振成像（MRI）造影剂或探针。这项研究的目的是设计造影剂，通过使用与生物相关的金属铁来产生强的MRI信号。这些铁基药物将以小分子复合物或纳米粒脂质体的形式存在。一类铁基药剂会以产生信号的形式稳定下来，而另一类只会在炎症的氧化条件下产生信号。该项目是有机、无机、生物化学和成像科学的结合。珍妮特·莫罗教授的小组在教育和培训研究生和本科生，包括那些在科学领域代表性不足的学生方面处于有利地位。涉及高中学生和他们的老师的推广活动将是资助项目的一部分，其目标是开发关于铁纳米颗粒制备和磁性质的实验室和讲座材料。铁(III)的核磁共振探测感兴趣的作为Gd的选择(3)配合物应用于临床的发展也响应造影剂登记的炎症疾病。拟议的研究将探索铁基MRI探针作为小分子或纳入脂质体制剂的合成，并将包括溶液和小鼠的研究。总体目标包括利用核磁弛豫色散（NMRD）获取水相互作用和电子弛豫过程的信息，通过研究纵向弛豫度（T1）对磁场强度的依赖，优化Fe（III）配合物作为弛豫剂。其次，Janet Morrow教授的团队在Fe（II）和Fe（III）的配位化学方面的专业知识使他们在解决开发对炎症相应的氧化过程有反应的MRI对比剂的挑战方面处于有利地位。配合物和脂质体制剂将作为响应性MRI探针在溶液中研究，在炎症过程中发现产生氧化剂的酶的存在。最后，在小鼠中的MRI研究将能够探索探针的生物分布，并为研究炎症影响组织作为长期目标提供机会。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 Chemical Structure, Dynamics & Mechanisms-B (CSDM-B) Program and the Chemical Measurement and Imaging (CMI) program of the Chemistry Division, Professor Janet Morrow and her team in the Department of Chemistry at the University of Buffalo, the State University of New York is developing new classes of magnetic resonance imaging (MRI) contrast agents or probes based on iron coordination complexes. The goal of this research is to design contrast agents that produce a strong MRI signal by using the biologically relevant metal, iron. These iron-based agents will be in the form of small molecule complexes or liposomal nanoparticles. One class of iron-based agents will be stabilized in the signal producing form and the other class will produce signal only under oxidizing conditions of inflammation. The project lies at the nexus of organic, inorganic, biological chemistry and imaging science. Professor Janet Morrow's group is well-positioned to educate and train graduate and undergraduate students including those underrepresented in science. Outreach activities involving high school students and their teachers will be part of the funded project with the goal of developing laboratory and lecture materials on the preparation and magnetic properties of iron nanoparticles. Fe(III)-based MRI probes are of interest as alternatives for Gd(III) complexes used in the clinic and also for the development of responsive contrast agents for the registration of inflammation found in disease states. The proposed research will explore the synthesis of iron-based MRI probes as small molecules or incorporated into liposomal agents and will include studies in solution and in mice. Overall goals include the optimization of Fe(III) coordination complexes as relaxation agents through the study of the magnetic field strength dependence of the longitudinal relaxivity (T1) by using nuclear magnetic relaxation dispersion (NMRD) to gain information on water interactions and electronic relaxation processes. Second, the expertise of Professor Janet Morrow's group in the coordination chemistry of both Fe(II) and Fe(III) places them in a strong position to address the challenges of developing MRI contrast agents that are responsive to oxidation processes corresponding to inflammation. Coordination complexes and liposomal agents will be studied as responsive MRI probes in solution in the presence of enzymes that generate oxidants found in inflammatory processes. Finally, MRI studies in mice will enable the exploration of biodistribution of the probe and provide opportunities for studying inflammation-impacted tissue as a long-term goal.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.