DNA-based nanodevices controlled by molecular and electronic inputs for diagnostic and drug delivery applications

DNA nanotechnology leverages nucleic acids to control the spatial and temporal distribution of matter, utilizing the specificity and predictability of Watson-Crick base pairing to create self-assembled nanostructures. This PhD thesis presents the development of DNA nanomachines based on novel structure-switching mechanisms. Traditional DNA nanomachines undergo input-induced conformational changes, typically triggered by nucleic acids, small molecules, proteins recognized by specific DNA/RNA sequences (aptamers), or environmental changes like temperature, light, or pH. To expand this range of triggering inputs, this research explores new methods to control and activate DNA-based nanomachines using molecular and electronic stimuli. The study involves designing, characterizing, and optimizing various DNA-based nanoswitches and nanomachines for applications in diagnostics, drug delivery, imaging, and cell biology. The first part of the thesis (Chapters 2, 3, and 4) introduces three classes of DNA nanomachines activated and controlled by specific antibodies and proteins for diagnostic and drug-delivery applications. Chapter 2 details a versatile sensing platform for the one-step detection of monovalent and multivalent macromolecular targets, including clinically relevant antibodies, potentially useful in point-of-care diagnostics and in vivo imaging. Chapters 3 and 4 describe two DNA-based nanomachines engineered to enable controlled release of molecular cargo, such as DNA strands or anti-cancer drugs, upon binding to specific antibodies or proteins. The second part of the thesis (Chapters 5 and 6) demonstrates the precise control of DNA-based nanodevices and nanoswitches using electronic inputs. Employing electronic inputs to control DNA-based nanodevices, combined with the affordability and potential miniaturization of electrochemical instruments, represents a significant advancement in DNA nanotechnology, paving the way for new and exciting developments. This PhD thesis marks an initial step toward utilizing diverse triggering inputs, both molecular and non-molecular, to activate and control DNA-based nanomachines and nanodevices, broadening their applicability across various fields.