Photo-Uncaging and Delivery of Bioactive Small Molecules

生物活性小分子的光解笼和递送

• 批准号: 1565702
• 负责人: Peter Ford
• 金额: $ 51.17万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1565702&HistoricalAwards=false
• 关键词: Photo; Uncaging; Delivery; Bioactive; Small

In this project funded by the Chemical Structure, Dynamics & Mechanisms B Program of the Chemistry Division, Professor Peter C. Ford of the Department of Chemistry and Biochemistry at the University of California, Santa Barbara is developing systems that can release bioactive small molecules when signaled by light. Small molecules such as nitric oxide (NO) and carbon monoxide (CO) play important roles in regulating functions such as blood pressure and inflammation. The ability to control the release of these small molecules in the body may also have therapeutic values in cancer treatment and wound healing. In this research, very small, metal containing particles are designed to bring NO, CO and other small molecules to specific sites in the body. Once at the site, the particles are exposed to light and release their "cargo". This targeted delivery of small molecules may eventually reduce the side effects of chemotherapy by lowering the dosage amount of certain drugs. The project involves aspects of synthetic inorganic and nanomaterial chemistry, mechanistic photochemistry and photophysics, as well as chemical biology. The graduate and undergraduate student researchers involved have the opportunity to make fundamental contributions to these fields and to broaden their scientific experience to be better positioned for contributing to a changing technical world. The researchers are also active in various outreach activities, including regular visitations to science classes at regional high schools to put a human face on the word "scientist" for an economically and ethnically diverse group of high school students. This project has three themes: (1) designing metal complexes conjugated to antennas that utilize deep tissue penetrating near-infrared (NIR) light as the excitation source; (2) developing carriers for these conjugates that target desired sites; and (3) mechanistic studies of the reactions of carbon disulfide (CS2) with various nucleophiles under biologically-relevant conditions and the design and photoreactions of potential CS2 precursors. The antennas include semi-conductor quantum dots and lanthanide doped upconverting nanoparticles that can be activated by multi-photon excitation at near infrared (NIR) wavelengths. Polymer-based nano- and micron-sized devices are as carriers with the above conjugates. Biological mechanisms such as targeting proteins and immune cells are recruited to deliver these conjugates to sites where NIR excitation leads to targeted release. The third theme is motivated by the possibilities that CS2 is an unrecognized regulator and/or that directed release has potential therapeutic value.

在这个由化学系化学结构、动力学和机制B计划资助的项目中，加州大学圣巴巴拉分校化学和生物化学系的彼得·C·福特教授正在开发能够在光发出信号时释放生物活性小分子的系统。一氧化氮(NO)和一氧化碳(CO)等小分子在调节血压和炎症等功能方面发挥着重要作用。控制这些小分子在体内释放的能力在癌症治疗和伤口愈合方面也可能具有治疗价值。在这项研究中，含有金属的非常小的颗粒被设计成将NO、CO和其他小分子带到身体的特定部位。一旦到达现场，这些颗粒就会暴露在光线下，并释放出它们的“货物”。这种靶向递送的小分子药物可能最终会通过降低某些药物的剂量来减少化疗的副作用。该项目涉及合成无机和纳米材料化学、机械光化学和光物理以及化学生物学的各个方面。参与的研究生和本科生研究人员有机会对这些领域做出根本贡献，并扩大他们的科学经验，以便更好地为不断变化的技术世界做出贡献。研究人员还积极参加各种外展活动，包括定期访问地区高中的科学课程，为经济和种族多样化的高中生群体展示“科学家”这个词的人性化面孔。该项目有三个主题：(1)设计与天线相连的金属络合物，利用深部组织穿透近红外(NIR)光作为激发源；(2)为这些络合物开发针对所需位置的载体；(3)二硫化碳(CS2)与各种亲核试剂在生物相关条件下的反应机理研究，以及潜在CS2前体的设计和光反应。这些天线包括半导体量子点和掺镧上转换纳米粒子，它们可以在近红外(NIR)波长下被多光子激发激活。以聚合物为基础的纳米和微米级器件作为载体与上述结合物。生物机制，如靶向蛋白质和免疫细胞，被招募来将这些偶联物输送到近红外激发导致靶向释放的位置。第三个主题的动机是CS2可能是一种未被识别的调节因子和/或定向释放具有潜在的治疗价值。