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

用于体内传感的基于环肽的纳米机器人的可扩展纳米制造

• 批准号: 1437177
• 负责人: Mingjun Zhang
• 金额: $ 28.89万
• 依托单位: Ohio State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1437177&HistoricalAwards=false
• 关键词: Scalable; Nanomanufacturing; Cyclic; Peptide; Based

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.

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。环肽是蛋白质链。纳米制造将涉及组装与基于 DNA 的适体缀合或连接的各种类型的基于环肽的纳米管。适体是与预先选定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反应条件下自组装单个环肽亚基而形成。核心体形成后，缀合的适体将充当传感和驱动组件。当目标生物标志物与适体结合时，会发生构象变化，从而使纳米机器人释放其有效负载。为了优化设计，将构建由肽亚基数量控制的不同直径的环肽库。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体将与纳米机器人结合并进行测试。为了扩大制造工艺，将研究相平衡方法、本体溶液自组装和逐层组装方法。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得到进一步优化。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，例如体内（活体）传感、疾病诊断和靶向药物输送。该研究将推动自组装生物分子科学的发展，这将影响纳米制造领域。通过这项研究学到的原理将适用于各种纳米级自组装过程，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。该项目将制定多项教育和推广计划，特别针对女性和少数民族学生。