Ultrasound-triggered release and activation of drugs and biomacromolecules from nucleic acid scaffolds

In the emerging field of polymer mechanochemistry the advantageous properties ofultrasound (US) can be exploited to control properties on a molecular level byrearranging or cleaving bonds site-specifically. For a successful and selective bondactivation by mechanical stress, a macromolecular framework is required thattransduces the force to the mechanochemically labile bond of the latent molecular motif(the mechanophore). For biomedical applications, the utilization of non-invasive US isparticularly beneficial, as it combines spatial and temporal control with easy regulationof the tissue penetration depth by varying frequency and energy through exposure time.While until now research in mechanochemistry mainly focused on understanding theforce-induced chemical transformations and their impact on material properties,utilization of site-selective bond-scission for drug activation in the field of medicineremained unexplored. In this context, we came up with two feasible ways to activatedrugs and proteins from either poly-nucleic acids or DNA-conjugated nanoparticles bythe treatment of ultrasound, aiming to find applications in the biomedical field. Notably,we presented the first molecular design to activate proteins and drugs from theirdeactivated aptamer-bound parent form by using mechanical force in the form ofultrasound