(3b) Harnessing Chaos: Rational Design of Nanoscale Surfaces for Cavitation-Based Imaging Agents, Nanomotors, and Protein Therapeutics.

Cavitation events, or the formation of a gas pocket in a liquid medium, can be highly destructive and disruptive. These events offer a unique opportunity to localize large amounts of energy using remote triggering. We have sought to understand how nanoscale surfaces can facilitate or inhibit cavitation by examining the structure-property relationships that give rise to efficient bubble nucleation. These approaches in turn underlie our new technologies in imaging, therapy, and protective coatings.

First, the formation of bubbles in solution can be used as efficient ultrasound contrast agents. Because of their high compressibility and low density, bubbles offer excellent contrast in aqueous media. However, microbubbles suffer from low stability and an inability to leave the bloodstream. In this work, we engineered functionalized silica nanoparticles that could facilitate the formation of transient microbubbles in response to an incoming acoustic wave.

Second, acoustic cavitation on nanoparticle surfaces gives rise to many therapeutic applications. Non-equilibrium bubble collapse is a violent process that concentrates both thermal and mechanical energy capable of not only killing cells but transporting nanoparticles through dense media such as extracellular matrix. Notably, the propulsion of nanoparticles can kill cells up to hundreds of microns away, thereby addressing transport limitations in solid tumors.

Third, we sought to rationally design surfaces that could retard cavitation as well. Solutions of protein therapeutics are known to form particulates upon impact and resulting cavitation. These particulates can in turn induce an anaphylactic response in patients, in some cases leading to patient death. Here, new coatings were applied to standard glass vials to reduce their tendency towards cavitation, thereby protecting the proteins in solution from irreversible aggregation.