(673a) Integration of Periodically Sequenced "Surftides" into Acoustically Active, Lipid-Shelled Microbubbles

The design of functional assemblies that possess both therapeutic properties, along with simultaneous diagnostic capabilities have become an emerging area of examination for site-specific drug delivery.  This presentation will describe our ongoing work to develop biomolecular assemblies that exhibit both of these characteristics.  We use microbubbles as multifunctional, biomimetic materials with a monolayer shell (i.e. lipids, polymer, protein) of surface-active components that encapsulates a gas core.  Due to the inherent compressibility of the gaseous interior, microbubbles are commonly used as contrast enhancing agents in conjunction with clinical ultrasound.  These materials have been shown to be effective in distinguishing between native tissue and vasculature, as the acoustic response of both tissue and bubble-rich vessels in the presence of ultrasonic pressure waves are dissimilar.  While microbubbles have been extremely useful in imaging applications these particles also serve as a platform for “theranostics”, coupling a targeting/therapeutic component to the system with the added benefit of an external triggering mechanism.  Our work focuses on exploiting the advantageous properties of the micrbubble system, while simultaneously incorporating rationally designed peptides that serve as model molecules for a class of highly functional molecules, proteins.  We hypothesize that the integration of peptides into the microbubbles will likely influence the phase behavior of the shell constituents, promoting the potential for functionality, possibly, at the expense of long-term stability and conventional bubble mechanics.  In this work, we investigate the partitioning of two rationally designed, “surftides” (surface-active peptides) into the lipid monolayer shell in order to investigate the impact of charge distribution on the surface-activity, adsorption into the bubble interface, and monolayer mechanics.  Furthermore, we aim to quantify the effect that the spacing of charged residues has on both secondary structure in solution and at the bubble interface using circular dichroism.  Lastly, we perform in vitro ultrasound measurements to determine the effect that the presence of peptides has on the particle stability and dissolution kinetics.