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.

项目摘要 合成聚合物的结构分散性对于其临床应用和监管批准至关重要。在这 项目，我们提出了水溶性离散瓶刷轴承交替聚合物的发展 磷脂和氟化共聚单体，使其能够作为无金属19 F MRI造影剂临床应用 剂.所提出的聚合物系统的新奇在于它结合了：1.离散分子量（如 与常规分散聚合物相反）; 2.分支架构的多功能性; 3.高水 磷酸胆碱基团的溶解性和生物相容性;以及4.外源性和化学性质相同的信号 19 F组。合理设计刷状聚合物结构、共聚单体序列， 预期亲脂-亲水平衡抑制信号增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靶向成像和传感策略。