NATURE NANODEVICES · Nature-inspired theranostic nanodevices for tumor imaging, early diagnosis and targeted drug-release

Late diagnosis and difficult treatment represent major obstacles in the fight against cancer. I propose here the development of self-regulated theranostic nanodevices supporting both early cancer diagnosis and targeted, tumor-cell-specific drug-release. Specifically, I will exploit the “designability” of nucleic acids to design and optimize molecular nanodevices that undergo binding-induced conformational changes upon target binding and, in doing so, signal the presence of a specific tumor marker or release a toxic therapeutic cargo. The inspiration behind my approach is derived from nature, which employs similar nanometer-scale protein and nucleic-acid-based “switches” as devices to detect –and respond to- specific molecules even against the complex background “noise” of the physiological environment. Furthering on this “nature-inspired” synthetic biology view I will also exploit naturally occurring regulatory mechanisms (e.g., allostery, cooperativity, etc.) to tune and edit the dose-response curve of these nanodevices, improve their analytical sensitivity, and optimize drug-release efficiency. In summary, I will use biomimetic “tricks’ taken directly from nature to move beyond the state-of-the-art of sensor design, with the goal being improved diagnostics and “smarter,” more effective drug delivery. Achieving these goals will require multidisciplinary expertise in the field of analytical chemistry, biophysics, electrochemistry, bioengineering, computational chemistry and synthetic biology. In my career I have demonstrated skills and expertise in similarly complex projects and in each of these challenging fields. Finally, the development of the proposed nanodevices will significantly impact the safety, compliance and efficacy of therapies and medical procedures bringing to scientific, technological and socio-economic benefits.