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.
