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: 10610352
• 负责人: DAVID S. LAWRENCE
• 金额: $ 72.08万
• 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/10610352
• 关键词: Address; Adverse effects; Attention; Behavior; Biochemistry; Biological; Cardiovascular system; Cell surface; Cells; Circulation; 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; Penetration; Peptides; Pharmaceutical Preparations; Phototherapy; Plasma; Positioning Attribute; Prodrugs; Property; Proteins; Reactive Oxygen Species; Reporting; Research; Site; Surface; System; Technology; Therapeutic; Therapeutic Agents; Tissues; Toxic effect; Treatment Efficacy; Vitamin B 12; absorption; aggressive therapy; analog; design; dosage; drug action; drug disposition; fluorophore; functional group; improved; in vivo; inhibitor; 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?

项目概要 使用光来激活患病部位的治疗剂具有以下优点： 通过精确的空间和时间控制进行积极的治疗，从而减少 尽管是光激活的前药，但在非预期部位可能会产生有害的副作用。 据报道，这些物种需要短波长（<450 nm）来激活。 然而，光的最大组织渗透发生在“组织的光学窗口”内 (600 – 900 nm)，远远超出现有光可裂解功能的波长范围 我们开发了一种新技术，可以将药物转化为光响应药物。 由循环红细胞传递的“光疗”。 研究计划旨在解决与光相关的几个基本问​​题 响应性治疗：（1）光捕获和药物释放的机制是什么？ 基于B12的分子支架，（2）优化的结构关系是什么 光捕获天线和 B12-药物键的光解之间的关系，(3) 是适用于这种光技术的治疗剂的范围，(4) 相对于标准光疗提供了增强的治疗窗口 注意，（5）激活波长与光强之间的关系是什么？ 治疗窗口？

项目成果

Taking phototherapeutics from concept to clinical launch.

将光疗从概念到临床启动。

• 发表时间: 2021
• 作者: Vickerman, Brianna M;Zywot, Emilia M;Tarrant, Teresa K;Lawrence, David S
• 通讯作者: Lawrence, David S

Taking phototherapeutics from concept to clinical launch.

将光疗从概念到临床启动。

• 发表时间: 2021-11
• 作者: Vickerman, Brianna M;Zywot, Emilia M;Tarrant, Teresa K;Lawrence, David S
• 通讯作者: Lawrence, David S

Assessment of Photoreleasable Linkers and Light-Capturing Antennas on a Photoresponsive Cobalamin Scaffold.

光响应钴胺素支架上的光可释放连接体和光捕获天线的评估。

• 发表时间: 2022-04-15
• 作者: Welfare, Joshua G.;Mortelliti, Michael J.;McGlade, Caylie A.;Hartman, Timothy W.;Dempsey, Jillian L.;Lawrence, David S.
• 通讯作者: Lawrence, David S.