CAREER: Multi-stimuli Responsive DNA-Nanoshells - Compartmentalizing Molecules at the Nanoscale for Enhanced Reaction Selectivity and Sensitivity

病毒已经进化出自毁机制，允许它们在进入正确的宿主时释放其内容。这些病毒被装饰着分子，当它们遇到某些生物系统中发现的特定酶时，就会触发它们的降解。康涅狄格大学杰西卡·鲁日教授的研究小组从病毒颗粒如何以高度特定的方式对环境做出反应中获得灵感，他们正在开发新的化学策略来合成非常小的贝壳，这种贝壳既可以可控地包裹小分子，又可以在复杂的混合物中对特定刺激做出反应而释放它们。这些策略对于开发更灵敏的生物传感器和更准确的药物输送系统非常重要。该项目为研究生和本科生提供纳米科学、化学合成和生物化学方面的多学科研究培训。此外，还发起了一项题为“促进好奇心”的倡议，以吸引整个康涅狄格州的高中教师和学生。通过与康涅狄格州大学早期学院体验计划的这一联合倡议，正在设计负担得起的实验室方案，重点是生物纳米科学的基本工具和技术。这些实验模块将根据特定高中的需求和资源进行单独定制，为学生提供这门令人兴奋的纳米材料课程的实践经验，并为他们未来与纳米技术和化学相关的职业做好准备。在大分子、超分子和纳米化学计划的支持下，Rouge Group正在开发新的化学交联策略，这些策略可以被结合到DNA纳米材料中，以控制其在复杂生物环境中的组装和拆卸。利用一种新的DNA-表面活性剂组装策略，产生与细胞和酶兼容的DNA纳米壳，本工作的主要目标是合成多肽和合成交联剂的组合，这种组合可以在生物系统中保持纳米材料的稳定性，同时对某些化学和生化刺激表现出选择性。这些刺激，包括温度和pH的变化，或暴露在特定的酶类中，将被用来控制小分子的释放，以启动化学反应和/或生化反应。通过这项工作，实现了以下目标：1)设计能够远程控制底物释放的热敏交联剂文库，2)设计用于检测DNA纳米壳局部环境的配体-货物通信方案，以及3)通过从多层肽交联DNA-纳米壳中逐步释放底物来控制溶液反应的选择性。DNA-纳米壳层内不同底物的划分将使团队能够研究不同分子在水体系中的释放速率和随后的反应速率。这一奖项反映了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。

Viruses have evolved self-destruct mechanisms that allow them to release their contents when they are inside the right host. The viruses are decorated with molecules that trigger their degradation when they encounter specific enzymes found within certain biological systems. Using inspiration from how virus particles respond to their environment in highly specific ways, the research group of Professor Jessica Rouge at the University of Connecticut is developing new chemical strategies to synthesize shells of very small size that can both controllably encapsulate small molecules and release them in response to specific stimuli in complex mixtures. Such strategies are important for developing more sensitive biological sensors and more accurate drug delivery systems. This project provides graduate and undergraduate students multidisciplinary research training in nanoscience, chemical synthesis, and biochemistry. In addition, an initiative entitled "Catalyzing Curie-osity" is launched to engage high school teachers and students throughout the state of Connecticut. Through this joint initiative with the UConn Early College Experience program, affordable lab protocols are being designed focusing on the fundamental tools and techniques of bio-nanoscience. These lab modules will be individually tailored to the needs and resources of specific high schools, giving students hands -n experience with this exciting class of nanomaterials and preparing them for future careers related to nanotechnology and chemistry. With the support of the Macromolecular, Supramolecular and Nanochemistry program, the Rouge Group is developing novel chemical crosslinking strategies that can be incorporated into DNA nanomaterials for controlling their assembly and disassembly in complex biological environments. Using a novel DNA-surfactant assembly strategy that generates DNA nanoshells compatible with cells and enzymes, the major goal of this work is to synthesize a combination of peptide and synthetic crosslinkages that can maintain the nanomaterials stability in biological systems while exhibiting selectivity for certain chemical and biochemical stimuli. These stimuli, including temperature and pH changes, or exposure to specific enzyme classes, will be used to gate the release of small molecules for initiating chemical and/or biochemical reactions. Through this work the following goals are addressed: 1) the design of a library of thermoresponsive crosslinkers that enables remotely controlled substrate release, 2) the design of ligand-cargo communication schemes for sensing the local environment of the DNA-nanoshells, and 3) control over solution reaction selectivity via stepwise substrate release from multi-layered peptide crosslinked DNA-nanoshells. Compartmentalization of different substrates within the DNA-nanoshell layers will allow the team to study release rates and subsequent reaction rates of diverse molecules in aqueous systems.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.