Gas vesicle-blood interactions enhance ultrasound imaging contrast

Abstract

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 a systemically injectable nanomaterial have been hindered by a lack of understanding of GVs’ interactions with blood components, which can significantly impactin vivoperformance. 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 vivoperformance. These results provide critical insights for the development of GVs as agents for nanomedicine.

50‐nm Gas‐Filled Protein Nanostructures to Enable the Access of Lymphatic Cells by Ultrasound Technologies

“…To this end, recent studies have shown that some immunogenicity exists for wild‐type GVs, as expected for bacteria‐derived protein sequences, and demonstrated that the biocompatibility of GVs can be substantially enhanced through surface coating, such as polyethylene glycol (PEG) modification. [ 66–69 ] Since 50 nm GVs use protein sequences originating from these wild‐type GVs, we anticipate a similar level of immunogenicity and opportunities for reducing immunogenicity through surface modification. Secondly, the ultrasound pressure and mechanical index needed to be determined for the efficient collapse of 50 nm GVs in in vivo applications.…”