Fast functionalization of ultrasound microbubbles using strain promoted click chemistry

Functionalization of microbubbles (MBs) is a difficult issue due to their unstable nature. Here we report a fast and versatile method using a strain promoted alkyne-azide cycloaddition (SPAAC) click reaction for microbubble functionalization. An azadibenzocyclooctyne (DBCO) group was first introduced onto the MB surface and then an azide group into the desired ligand. Without any initiators or catalysts, essential click ligation occurred within 1 min and a majority of the reaction completed in 5 min at 37 °C. This fast ligation shortens the microbubble reaction time and preserves essential amounts of microbubbles for further in situ imaging and delivery of therapeutics.