POLYMERIC ELECTRON PARAMAGNETIC RESONANCE PROBES FOR REAL-TIME MONITORING OF TISSUE VASCULARIZATION

用于实时监测组织血管化的聚合物电子顺磁共振探头

• 批准号: 9811147
• 负责人: Jianjun Guan
• 金额: $ 15.42万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-08 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9811147
• 关键词: POLYMERIC; ELECTRON; PARAMAGNETIC; RESONANCE; PROBES

Program Director/Principal Investigator (Last, First, Middle): GUAN, JIANJUN Project Summary The objective of this proposal is to create bioeliminable and injectable hydrogel-based electron paramagnetic resonance (EPR) probes that can be implanted for the real-time and long-term measurement of tissue oxygen (O2) concentration. The purpose is to monitor the ischemic tissue vascularization process during therapy. Ischemic diseases, resulting from reduced blood supply, lead to serious damage and injury of various tissues and organs. The primary therapeutic goal for ischemic diseases is to vascularize the ischemic tissues to restore blood flow. To quickly, conveniently, and accurately evaluate the efficacy of the therapy, real-time and reproducible monitoring of tissue O2 concentration changes at the same tissue location by a minimally invasive or non-invasive spectroscopic approach represents a compelling strategy. However, this cannot be achieved by any clinically available approaches. Current approaches are either unable to provide real-time and long-term measurements under ischemic conditions or invasive. Among the different techniques for tissue O2 concentration measurement, EPR has the potential to achieve this goal. EPR has distinct advantages over other techniques, such as the ability to measure tissue O2 concentration without consuming O2, and to provide absolute values even at low O2 concentration environment. However, until now there is a lack of suitable EPR probes that can maintain a consistent concentration in tissues for an extended period (≥ 4 weeks), and can be implanted and/or retrieved by a minimally invasive approach. The proposed work addresses the critical need for bioeliminable, non-toxic, and long-lasting EPR probes that can be implanted by a minimally invasive approach for the long-term monitoring of tissue O2 concentration. This is highly novel and similar EPR probes have not been developed previously. The proposed hydrogel-based EPR probes will not only be injectable and bioeliminable, but also feature a fast gelation rate, a slow weight loss rate, high O2 permeability, and high EPR sensitivity. The injectable hydrogels can be implanted into tissues by a minimally invasive injection approach. The hydrogel-based EPR probes will have high molecular weight, and this will overcome the toxicity issue of commonly used small molecule EPR probes. Furthermore, they can be removed from the body after becoming water soluble by hydrolysis of side groups, thereby eliminating the need for retrieval. The hydrogels will be designed to have high gelation rate to achieve high retention in tissues. The probes with slow weight loss rate will maintain the EPR signal intensity for an extended period of time while retaining in a certain tissue location, allowing for long-term monitoring of O2 concentration. The high O2 permeability and EPR sensitivity will ensure that a small change in O2 concentration can be monitored in real-time. AIM #1 will create bioeliminable and injectable hydrogel-based EPR probes with a fast gelation rate, a slow weight loss rate, high oxygen permeability, and high EPR sensitivity. AIM #2 will test the hypothesis that the developed hydrogel-based EPR probe will allow continuous monitoring of tissue oxygen concentration using an ischemic limb model. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page

项目主任/首席研究员（后、一、中）：管建军 项目概要 该提案的目标是创建可生物消除和可注射的基于水凝胶的电子顺磁 可植入实时、长期测量组织氧 (O2) 的共振 (EPR) 探针 目的是监测治疗期间缺血组织的血管化过程。 由于血液供应减少而引起的疾病会导致各种组织和器官的严重损害和损伤。 缺血性疾病的主要治疗目标是使缺血组织血管化以恢复血流。 快速、方便、准确地评估治疗效果，实时、可重复监测 通过微创或无创光谱分析同一组织位置的组织 O2 浓度变化 然而，任何临床可用的方法都无法实现这一点。 当前的方法无法提供实时和长期的测量。 缺血性病症或侵袭性病症。 在组织 O2 浓度测量的不同技术中，EPR 有潜力实现这一目标 EPR 与其他技术相比具有明显的优势，例如测量组织 O2 浓度的能力。 不消耗O2，并且即使在低O2浓度环境下也能提供绝对值。 现在缺乏合适的 EPR 探针可以在组织中长时间保持一致的浓度 周期（≥ 4 周），并且可以通过微创方法植入和/或取出。 拟议的工作解决了对可生物消除、无毒且持久的 EPR 探针的迫切需求 可以通过微创方法植入，用于长期监测组织中的 O2 浓度。 之前尚未开发出高度新颖且类似的 EPR 探针。 探针不仅是可注射和可生物消除的，而且还具有快速凝胶速率、缓慢失重速率、 高 O2 渗透性和高 EPR 敏感性可通过注射水凝胶植入组织中。 基于水凝胶的 EPR 探针将具有高分子量，这将是微创注射方法。 克服了常用小分子 EPR 探针的毒性问题，而且可以将它们从其中去除。 通过侧基水解而溶于水后，可被身体吸收，从而消除了回收的需要。 水凝胶将被设计成具有高凝胶率，以实现在组织中的高保留。 减重率将在较长时间内维持 EPR 信号强度，同时保留在一定的范围内。 组织位置，允许长期监测 O2 浓度 高 O2 渗透性和 EPR 敏感性。 将确保可以实时监测 O2 浓度的微小变化。 AIM #1 将创建可生物消除和可注射的基于水凝胶的 EPR 探针，具有快速凝胶速率、缓慢的凝胶速率 减重率高、透氧率高、EPR敏感性高。 AIM #2 将测试所开发的基于水凝胶的 EPR 探针将允许连续监测的假设 使用缺血肢体模型测量组织氧浓度。 OMB 编号 0925-0001/0002（修订版 08/12 已批准至 8/31/2015） 页面延续格式页面