Gas Vesicle–Blood Interactions Enhance Ultrasound Imaging Contrast

Gas vesicles (GVs)
are genetically encoded, air-filled protein
nanostructures of broad interest for biomedical research and clinical
applications, acting as imaging and therapeutic agents for ultrasound,
magnetic resonance, and optical techniques. However, the biomedical
applications of GVs as systemically injectable nanomaterials have
been hindered by a lack of understanding of GVs’ interactions
with blood components, which can significantly impact in vivo behavior. Here, we investigate the dynamics of GVs in the bloodstream
using a combination of ultrasound and optical imaging, surface functionalization,
flow cytometry, and mass spectrometry. We find that erythrocytes and
serum proteins bind to GVs and shape their acoustic response, circulation
time, and immunogenicity. We show that by modifying the GV surface
we can alter these interactions and thereby modify GVs’ in vivo performance. These results provide critical insights
for the development of GVs as agents for nanomedicine.