Discrete Polymer-based, Metal-free MRI Contrast Agents

离散聚合物基、无金属 MRI 造影剂

• 批准号: 10715368
• 负责人: Jimmy Lawrence
• 金额: $ 36.44万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715368
• 关键词: Architecture; Blood Vessels; Chemicals; Clinical; Contrast Media; Deposition; Development; Diagnosis; Equilibrium; Fibrosis; Hypersensitivity; Magnetic Resonance Imaging; Metals; Molecular Weight; Monitor; Noise; Phospholipids; Phosphorylcholine; Polymers; Renal clearance function; Signal Transduction; System; Tissues; Water; biomaterial compatibility; blood damage; clinical application; hydrophilicity; in vivo; lipophilicity; rational design; targeted imaging; tumor; water solubility

Project Summary Structural dispersity in synthetic polymers is paramount for their clinical use and regulatory approval. In this project, we propose the development of water-soluble discrete bottlebrush polymers bearing alternating phospholipid and fluorinated comonomers to enable their clinical applications as metal-free19F MRI contrast agents. The novelty of the proposed polymer system is that it combines: 1. discrete molecular weight (as opposed to conventional disperse polymers); 2. multifunctionality of branched architectures; 3. high water solubility and biocompatibility of phosphorylcholine groups; and 4. exogenous and chemically identical signal of19F groups. Rational design of the brush polymer architecture, comonomer sequence, and lipophilic-hydrophilic balance is anticipated to suppress signal broadening and yield discrete synthetic polymer-based platforms that can be further extended to other targeted imaging and sensing strategies.

项目概要 合成聚合物的结构分散性对于其临床使用和监管批准至关重要。在这个 项目中，我们建议开发水溶性离散瓶刷聚合物轴承交替 磷脂和氟化共聚单体使其能够作为无金属 19F MRI 造影剂进行临床应用 代理。所提出的聚合物体系的新颖之处在于它结合了： 1. 离散分子量（如 与传统的分散聚合物相反）； 2. 分支架构的多功能性； 3、高水位 磷酸胆碱基团的溶解度和生物相容性； 4. 外源且化学相同的信号 19F组。合理设计刷状聚合物结构、共聚单体序列和 亲脂-亲水平衡预计会抑制信号展宽并产生离散的合成 基于聚合物的平台，可以进一步扩展到其他目标成像和传感策略。