Scalable Nanomanufacturing of Cyclic Peptide-Based Nanorobots for In Vivo Sensing

这笔赠款为开发纳米制造平台提供资金，用于制造用于生物医学应用的基于环肽的纳米机器人。环肽是一种蛋白质链。纳米制造将包括组装各种类型的基于环肽的纳米管，这些纳米管与基于DNA的适配子结合或连接。适配子是与预先选择的靶点结合的生物分子。纳米机器人的核心体将在受控反应条件下由单个环肽亚基自组装而成。在核心体形成后，共轭适配子将作为传感和执行元件。当靶向生物标志物与适体结合时，构象发生变化，允许纳米机器人释放它们的有效载荷。为了优化设计，将构建一个由多肽亚单位数量控制的不同直径的环多肽文库。为了进一步证明该方法的模块化，与特定疾病相关的各种生物标记物的适体将被连接到纳米机器人上并进行测试。为了扩大制备过程，将研究相平衡法、体液自组装和逐层组装方法。在原型制造后，纳米制造工艺将在可靠性、成品率和制造效率方面进一步优化。这项研究的结果将导致制造各种生物医学应用的纳米使能机器人，如活体(活体)感知、疾病诊断和靶向药物输送。这项研究将推进自组装生物分子的科学，这将对纳米制造领域产生影响。通过这项研究了解到的原理将适用于各种纳米级的自组装过程，这是自下而上制造纳米制造的关键步骤。一旦制造工艺得到优化，医学界将从纳米机器人中受益匪浅。该项目将开发几个教育和外展项目，特别是针对女性和少数族裔学生。

This grant provides funding for the development of a nanomanufacturing platform for fabricating cyclic peptide-based nanorobots for biomedical applications. Cyclic peptides are protein chains. The nanomanufacturing will involve assembling various types of cyclic peptide-based nanotubes conjugated or connected with DNA-based aptamers. Aptamers are biological molecules that bind to pre-selected targets. The core body of the nanorobots will be formed by self-assembling individual cyclic peptide subunits under controlled reaction conditions. After the core body has been formed, the conjugated aptamers will serve as the sensing as well as actuating components. Upon binding of a targeted biomarker to the aptamers, a conformational change takes place allowing the nanorobots to release their payload. In an effort to optimize the design, a library of cyclic peptides with varying diameters, controlled by the number of peptide subunits will be fabricated. To further demonstrate the modularity of the approach, aptamers for a variety of biomarkers related to specific diseases will be conjugated to the nanorobots and tested. To scale-up the fabrication process, phase equilibrium method, self-assembly in bulk solution, and layer-by-layer assembly method will be examined. After prototype fabrication, the nanomanufacturing process will be further optimized in terms of reliability, yield and manufacturing efficiency.The results of this research will lead to manufacturing of nano-enabled robots for a variety of bio-medical applications, such as, in vivo (living subject) sensing, disease diagnosis, and targeted drug delivery. The research will advance the science of self-assembled bio-molecules, which will impact the field of nanomanufacturing. The principles learned through this research will be applicable to various nano-scale self-assembly processes which are a key step for bottom-up nanomanufacturing. Once the fabrication process is optimized, the medical community will benefit greatly from the nanorobots. The project will develop several education and outreach programs, especially targeting female and minority students.