Controlling the activity of antibiotics by ultrasound

Current therapy with antibiotics suffers from emerging drug resistance and unwanted side effects in part as a result of improper administration and lack of drug selectivity. The implementation of targeting and activation mechanisms is a promising strategy allowing the spatial and temporal control over drug activity to circumvent these issues. Over the last decades, various approaches and drug delivery systems were developed to increase drug efficacy while reducing side-effects. However, many of these efforts were limited by poor selectivity, low loading capacity, leakage, or systemic side effects. It is hence highly desirable to develop systems that overcome these shortcomings while offering remote control over on-site drug activity, regardless of the selected target, thus resulting in a more effective and precise treatment. The recent development of polymer mechanochemistry provides possibility to achieve the spatial and temporal control over drug activity with ultrasound. The overall goal of the work described in this thesis was to design and construct new mechanophores, using site-selective bond-scission for drug activation in the field of medicine by ultrasound to increase antibiotic efficacy while reducing side-effects.