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

This grant provides funding for the development of a scalable nanomanufacturing platform to fabricate cyclic peptide-based nanorobots for biomedical applications, such as in vivo sensing, disease diagnosis, and targeted drug delivery. The nanomanufacturing platform will be used to assemble various types of cyclic peptide-based nanotubes conjugated with DNA-based aptamers. 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, aptamers will be conjugated to the open ends of the nanotubes, and serve as a sensing and actuating components. Upon binding of a target 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.