Collaborative Research: Accessing the Near Infrared Transparency Window for Triggered Delivery with Singlet Oxygen-Degradable Nanomaterials

合作研究：利用近红外透明窗口触发单线态氧可降解纳米材料的传递

• 批准号: 2003341
• 负责人: Samuel Thomas
• 金额: $ 31万
• 依托单位: Tufts University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2003341&HistoricalAwards=false
• 关键词: Collaborative; Research; Accessing; Near; Infrared

Non-Technical AbstractNano-sized materials that disassemble on demand can release therapeutic agents to sites where they are most needed. Light is an especially promising tool for triggering this on-demand carrier disintegration: it can pass through many barriers, be directed to precise locations, and be switched on and off easily. Most current biologically relevant technologies use high energy ultraviolet (UV) and visible light that do not penetrate tissue significantly. The research groups of Professor Samuel Thomas at Tufts University and Professor Vincent Rotello at the University of Massachusetts Amherst are working to overcome this limitation in therapeutic delivery by designing, developing, and understanding the ability of nano-sized materials to disintegrate upon exposure to low energy near-infrared (NIR) light. NIR light penetrates tissue to far greater depths than UV or visible light, providing access to new biological applications. They will gain understanding into how chemical design influences nanomaterial response to NIR light, and these materials will be further elaborated to target and deliver therapeutics to both cancer cells and bacterial biofilms. This research has the potential to benefit society through creation of new nanomaterials that harness NIR light to selectively deliver drugs and mitigate harmful side effects. Beyond the hands-on interdisciplinary training that this research provides to more graduate students, this project also provides targeted support for disadvantaged high school students to undertake research through the Tufts Summer Research Experience, thereby broadening participation in the STEM disciplines.Technical AbstractWith support from the Biomaterials Program of the NSF Division of Materials Research, the goal of this research is to establish the ability of micelles in vitro to be degraded by singlet oxygen prepared in situ using NIR light. The overall project goal is to understand how chemical structures and polymer assemblies influence key individual chemical and physical material characteristics relevant to drug delivery. The first phase of this project will be to prepare and characterize polymers and micelles with a range of singlet oxygen-cleavable linkers, reactivities, and polymer topologies. The second phase of this project will be to understand how chemical structure and nanomaterial composition determines loading of cargo, stability in serum, photodegradation, and triggered release. The third stage of this project will evaluate the in vitro cytotoxicity and anti-bacterial activity of cargo-loaded NIR-degradable micelles. Further extension of this understanding of fundamental structure-property relationships will include micelles with targeting groups on their surfaces such as the RGD motif for cancer cells and quaternary ammonium cations for bacterial biofilms. Overall, this work has the potential to improve the efficacy of light-responsive drug-delivery systems, and in a broader context, advance the field of stimuli-responsive biomaterials by correlating chemical structures and their assemblies with loading, release, and in vitro activity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

非技术摘要纳米尺寸的材料可以按需分解，从而将治疗剂释放到最需要的部位。光是触发这种按需载体分解的特别有前途的工具：它可以穿过许多障碍，被引导到精确的位置，并且很容易打开和关闭。大多数当前的生物相关技术使用不显著穿透组织的高能紫外线（UV）和可见光。塔夫茨大学的Samuel托马斯教授和马萨诸塞州阿默斯特大学的Vincent Rotello教授的研究小组正在努力通过设计、开发和理解纳米尺寸材料在暴露于低能量近红外（NIR）光时分解的能力来克服治疗递送中的这种限制。近红外光穿透组织的深度远大于紫外线或可见光，为新的生物应用提供了途径。他们将了解化学设计如何影响纳米材料对近红外光的反应，这些材料将进一步细化，以靶向癌细胞和细菌生物膜并提供治疗。这项研究有可能通过创造新的纳米材料来造福社会，这些纳米材料利用近红外光选择性地输送药物并减轻有害的副作用。除了这项研究为更多的研究生提供动手的跨学科培训外，该项目还为处境不利的高中生提供有针对性的支持，通过塔夫茨夏季研究经验进行研究，从而扩大对STEM学科的参与。技术摘要在NSF材料研究部生物材料计划的支持下，本研究的目的是确定胶束在体外被使用NIR光原位制备的单线态氧降解的能力。总体项目目标是了解化学结构和聚合物组装如何影响与药物输送相关的关键个体化学和物理材料特性。该项目的第一阶段将是制备和表征具有一系列单线态氧可裂解连接体、反应性和聚合物拓扑结构的聚合物和胶束。该项目的第二阶段将是了解化学结构和纳米材料成分如何决定货物的装载，血清中的稳定性，光降解和触发释放。本项目的第三阶段将评估负载近红外可降解胶束的体外细胞毒性和抗菌活性。这种对基本结构-性质关系的理解的进一步扩展将包括在其表面上具有靶向基团的胶束，例如用于癌细胞的RGD基序和用于细菌生物膜的季铵阳离子。总的来说，这项工作有可能提高光响应药物递送系统的功效，并在更广泛的背景下，通过将化学结构及其组装与负载，释放，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查进行评估，被认为值得支持的搜索.