Polymer Mechanochemistry Using Ultrasound: From Fundamental Reactivity to Controlled Drug Delivery

Polymer mechanochemistry harnesses mechanical force to drive specific chemical transformations in stress-sensitive molecules known as mechanophores. Through judicious chemical design, these force-driven reactions have enabled functional polymeric materials capable of sensing, self-healing, and catalysis. Research in this field encompasses expanding the mechanophore repertoire, elucidating the fundamental principles governing mechanically induced reactivity, and translating force-responsive systems into practical applications. This thesis advances the field by contributing both fundamental insight and applied functionality in mechanophore activation under ultrasonication, with a particular focus on controlled drug release in biological environments. First, we develop an improved methodology for characterizing mechanophore reactivity, addressing sensitivity limitations in sonication experiments and, combined with computational modeling, revealing underlying principles that govern force-induced bond activation. Separately, we establish a synergistic platform that couples cargo-releasing mechanophores with biocompatible focused ultrasound, enabling controlled release of a fluorophore and a chemotherapeutic agent under physiological conditions. Finally, we demonstrate mechanochemically triggered drug delivery in vivo and validate this process using an inducible protein-expression system as a biological readout, achieving the first constructive modulation of cellular function enabled by covalent polymer mechanochemistry. Together, these studies deepen the fundamental understanding of mechanophore reactivity and illustrate the substantial biomedical potential of mechanochemical approaches using ultrasound activation.