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

这笔赠款为开发用于制造生物医学应用的基于环肽的纳米机器人的纳米制造平台提供资金。环肽是蛋白质链。纳米制造将涉及组装各种类型的基于环肽的纳米管，这些纳米管与基于DNA的适体缀合或连接。适体是与预先选择的靶标结合的生物分子。纳米机器人的核心体将通过在受控的反应条件下自组装单个环状肽亚基来形成。在核心体形成后，缀合的适体将用作感测以及致动组分。在靶向生物标志物与适体结合后，发生构象变化，允许纳米机器人释放其有效载荷。为了优化设计，将制造由肽亚基的数量控制的具有不同直径的环肽文库。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志物的适体将与纳米机器人结合并进行测试。为了扩大制造过程，相平衡方法，在本体溶液中的自组装，和逐层组装方法将被检查。在原型制造完成后，纳米制造工艺将在可靠性、产量和制造效率方面进一步优化。这项研究的结果将导致制造用于各种生物医学应用的纳米机器人，例如，活体（活体）传感、疾病诊断和靶向药物递送。这项研究将推进自组装生物分子的科学，这将影响纳米制造领域。通过这项研究所学到的原理将适用于各种纳米尺度的自组装过程，这是自下而上的纳米制造的关键步骤。一旦制造过程得到优化，医学界将从纳米机器人中受益匪浅。该项目将制定若干教育和推广方案，特别是针对女生和少数民族学生。

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.