This research addresses the National Academy of Engineering’s Grand Challenge to engineer better medicines by developing new approaches that will ultimately allow rapid assessment of the genetic profiles in patients and the release of personalized drug cocktails. Our approach is to incorporate DNA “strand displacement” biosensing designs within polymer nanocarriers such that the DNA interface controls nanocarrier stability. Recognition of specific RNA or DNA sequences will result in a strand displacement reaction that destabilizes the nanocarrier and allows the release of encapsulated drugs or diagnostics. The major milestones in this work include the design of DNA strand displacement designs sensitive to breast cancer-specific RNAs; incorporation of these DNA duplexes within block polymer micelles; establishment of the specificity and efficacy of RNA-mediated nanocarrier disassembly; addition of cancer cell-targeting peptides on the surface of the nanocarriers; and establishment of selective cellular uptake and efficient cargo (dye) release in breast cancer cells.
Project 3. Design of RNA-triggered Disassembly Mechanisms in Multi-responsive Polymer Nanocapsules for Personalized Physiological Profiling and Tailored Therapeutics (NSF)
