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

非技术摘要按需分解的纳米材料可以将治疗剂释放到最需要它们的地方。光是触发这种按需载体解体的一个特别有前途的工具：它可以穿过许多障碍，被定向到准确的位置，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的是不会明显穿透组织的高能紫外线(UV)和可见光。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大学的文森特·罗特洛教授的研究小组正在通过设计、开发和了解纳米材料在暴露于低能量近红外线(NIR)光下分解的能力来克服这一限制。近红外光比紫外线或可见光穿透组织的深度要大得多，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药物。这项研究有可能通过创造新的纳米材料来造福社会，这种材料利用近红外光选择性地传递药物并减轻有害的副作用。除了这项研究为更多研究生提供的实践跨学科培训外，该项目还为贫困高中生提供有针对性的支持，让他们通过塔夫茨暑期研究体验进行研究，从而扩大对STEM学科的参与。技术摘要在美国国家科学基金会材料研究部生物材料计划的支持下，本研究的目标是建立体外胶束通过使用近红外光原位制备的单线态氧进行降解的能力。该项目的总体目标是了解化学结构和聚合物组装体如何影响与药物输送相关的关键个别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物、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组成如何决定货物的装载量、血清中的稳定性、光降解和触发释放。该项目的第三阶段将评估载货近红外可降解胶束的体外细胞毒性和抗菌活性。对基本结构-性质关系的这种理解的进一步扩展将包括其表面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盐阳离子。总体而言，这项工作有可能提高光响应性药物递送系统的效率，并在更广泛的背景下，通过将化学结构及其组件与加载、释放和体外活性相关联来推动刺激响应性生物材料领域的发展。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.