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

这项拨款为纳米制造平台的开发提供资金，用于制造生物医学应用的环肽基纳米机器人。环肽是蛋白质链。纳米制造将包括组装各种类型的环肽基纳米管，这些纳米管与基于dna的适配体偶联或连接。适配体是结合预先选择的目标的生物分子。纳米机器人的核心体将在受控的反应条件下由单个环肽亚基自组装而成。核心体形成后，共轭适配体将作为传感元件和驱动元件。当目标生物标记物与适体结合时，就会发生构象变化，从而使纳米机器人释放其有效载荷。为了优化设计，将制作一个由肽亚基数量控制的不同直径的环状肽库。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志物的适配体将被结合到纳米机器人上并进行测试。为了扩大制造过程，相平衡法，在散装溶液中自组装和逐层组装方法将被检查。原型制造完成后，纳米制造工艺将在可靠性、良率和制造效率方面进一步优化。该研究结果将导致制造纳米机器人，用于各种生物医学应用，如体内（活体）传感、疾病诊断、靶向药物输送。该研究将推动生物分子自组装科学的发展，并将对纳米制造领域产生影响。通过本研究获得的原理将适用于各种纳米级自组装工艺，这是自下而上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推广项目，特别是针对女性和少数民族学生。

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.