Design and Application of Photoresponsive Modules in Circulating Erythrocytes

循环红细胞光响应模块的设计与应用

• 批准号: 10208350
• 负责人: DAVID S. LAWRENCE
• 金额: $ 56.21万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10208350
• 关键词: Address; Adverse effects; Attention; Behavior; Biochemistry; Biological; Blood Circulation; Cardiovascular system; Cell surface; Cells; Clinical Trials; Combined Modality Therapy; Disease; Drug Delivery Systems; Drug Kinetics; Elements; Enzymatic Biochemistry; Erythrocytes; Eye; Face; Generations; Half-Life; Light; Malignant Neoplasms; Mediating; Metabolic; Metabolism; Modification; Molecular; Optics; Organism; Parents; Penetrance; Peptides; Pharmaceutical Preparations; Phototherapy; Plasma; Positioning Attribute; Prodrugs; Property; Proteins; Reactive Oxygen Species; Reporting; Research; Site; Structure; Surface; System; Technology; Therapeutic; Therapeutic Agents; Time; Tissues; Toxic effect; Treatment Efficacy; Vitamin B 12; aggressive therapy; analog; base; design; dosage; drug action; drug disposition; fluorophore; functional group; improved; in vivo; interest; new technology; peptide drug; photolysis; programs; scaffold; side effect; small molecule; small molecule therapeutics; standard of care; targeted delivery; targeted treatment; therapeutic protein; water solubility

Project Summary The use of light to activate therapeutic agents at diseased sites offers the advantage of aggressive treatment with exquisite spatial and temporal control, thereby reducing potential deleterious side effects at unintended sites. Although photo-activated pro-drugs have been reported, these species require short wavelengths (<450 nm) for activation. However, maximal tissue penetrance by light occurs within the “optical window of tissue” (600 – 900 nm), well beyond the wavelength range of existing photo-cleavable functional groups. We’ve developed a new technology that transforms drugs into light responsive “phototherapeutics” that are conveyed by circulating erythrocytes. The proposed research program seeks to address several fundamental questions associated with light responsive therapeutics: (1) What is the mechanism of light capture and drug release in the B12-based molecular scaffolds, (2) what is the optimized structural relationship between the light capturing antennas and the photolysis of the B12-drug bond, (3) what is the scope of therapeutic agents that are amenable to this photo-technology, (4) do phototherapeutics furnish an enhanced therapeutic window relative to the standard of care, and (5) what is the relationship between the activation wavelength and the therapeutic window?

项目摘要 使用光激活患病现场的治疗剂的优势 具有独家空间和临时控制的积极治疗，从而减少 意外地点的潜在有害副作用。虽然光激活的亲毒品 已经报道了这些物种需要短波长（<450 nm）才能激活。 但是，在“组织的光学窗口”中发生最大的组织渗透性。 （600 - 900 nm），远远超出了现有的可裂解功能的波长范围 组。我们已经开发了一种新技术，将药物转化为轻度反应 通过循环红细胞传达的“光疗法”。提议 研究计划旨在解决与光有关的几个基本问​​题 反应疗法：（1）在 基于B12的分子支架，（2）优化的结构关系是什么 在捕获天线的光和B12-rug键的光解之间，（3）什么 是该光学技术可以适应的理论代理的范围，（4）do 光疗法提供了相对于标准的增强的治疗窗口 护理和（5）激活波长与 治疗窗口？