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

【非技术】纳米级材料可以根据需要分解，从而将治疗剂释放到最需要的部位。光是触发这种按需载流子分解的一个特别有前途的工具：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。目前大多数与生物学相关的技术使用高能紫外线和可见光，这些光不会明显穿透组织。塔夫茨大学的塞缪尔·托马斯教授和马萨诸塞大学阿默斯特分校的文森特·罗泰罗教授的研究小组正在通过设计、开发和理解纳米材料在低能量近红外（NIR）光下分解的能力，努力克服治疗递送中的这一限制。近红外光穿透组织的深度远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，以靶向和传递治疗癌细胞和细菌生物膜。这项研究有潜力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来选择性地输送药物并减轻有害的副作用。除了本研究为更多研究生提供的跨学科实践培训外，该项目还为弱势高中学生提供有针对性的支持，让他们通过塔夫茨大学暑期研究体验项目进行研究，从而扩大STEM学科的参与度。技术摘要：在美国国家科学基金会材料研究部生物材料项目的支持下，本研究的目标是建立利用近红外光原位制备单线态氧在体外降解胶束的能力。该项目的总体目标是了解化学结构和聚合物组件如何影响与药物输送相关的关键单个化学和物理材料特性。该项目的第一阶段将是用一系列单线态氧可切割连接剂、反应性和聚合物拓扑制备和表征聚合物和胶束。该项目的第二阶段将是了解化学结构和纳米材料组成如何决定货物装载，血清稳定性，光降解和触发释放。本项目第三阶段将对载货nir可降解胶束的体外细胞毒性和抗菌活性进行评价。进一步扩展对基本结构-性质关系的理解将包括胶束表面的靶向基团，如癌细胞的RGD基序和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反应性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、释放和体外活性联系起来，推进刺激反应性生物材料领域。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.