(489af) Engineering Microbubbles with the Buried-Ligand Architecture for Tumor Targeting

Ultrasound allows sensitive, real-time in vivo imaging and has the advantages of being low-cost and portable. However, current clinical non-contrast ultrasound does not offer the ability to detect vascular structures based on their molecular signatures. Previous research has shown great promise for microbubbles to be used as targeted ultrasound contrast agents for molecular imaging applications. When processes with targeted microbubbles, ultrasound imaging will have the power to detect disease with specific molecular biomarkers, such as angiogenesis and inflammation, in addition to the enhanced sensitivity and contrast image quality.

One microbubble structure invented by Borden et al. (Biomaterials, 2008) used a buried-ligand architecture (BLA) where the targeted ligands were attached to the shorter poly(ethylene glycol) (PEG) chains and buried by an overbrush layer of longer chains. The ligand was revealed to the endothelium by oscillation in the acoustic field and became buried again after the end of the ultrasound pulse. The novel design provided a stealth stimulus-responsive ultrasound contrast agent with reduced immunogenicity, but without loss in microbubble binding efficiency. Results will be pretend on how different design parameters, such as ligand size and concentration, relative PEG chain length and PEG surface coverage density, affect the overall performance of BLA microbubbles in terms of immunogenicity and adhesion efficiency. Ultimately, a stealth ultrasound molecular imaging agent is designed and optimized for tumor targeting applications.