Abstract: Systems and methods for activating mechanochemical reactions remotely using biocompatible ultrasound in the presence of gas-filled structures are described. The collapse of gas-filled structures is achieved using biocompatible ultrasound. In turn, collapse of the gas-filled structures can mechanochemically activate mechanophore-functionalized polymers in solution. Mechanochemical activation of mechanophore-functionalized polymers under physiological conditions can trigger the release and/or delivery of a variety of cargos with the spatial and temporal precision and deep tissue penetration afforded by focused ultrasound.