Design and Application of Photoresponsive Modules in Circulating Erythrocytes

项目摘要 在患病部位使用光来激活治疗剂提供了以下优点： 积极的治疗与精致的空间和时间控制，从而减少 在非预期部位的潜在有害副作用。虽然光活化前药 已经报道，这些物质需要短波长（<450 nm）用于活化。 然而，光对组织的最大穿透发生在“组织的光学窗口”内。 (600- 900 nm），远远超出现有光可裂解官能化的波长范围。 组我们开发了一种新技术， 通过循环红细胞输送的“光疗剂”。拟议 一项研究计划试图解决与光有关的几个基本问题 反应疗法：（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，（3）什么 是适用于这种光技术的治疗剂的范围，（4）确实 光疗法提供了相对于标准的增强的治疗窗口， 关心，和（5）什么是激活波长之间的关系和 治疗窗？

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?