Surface-engineered bio-manufactured gas vesicles for multimodal imaging of glioma

Integrated imaging techniques offer enhanced medical insights into the central nervous system by combining different modalities. In glioma diagnosis, the challenge often lies in delivering contrast agents effectively across the blood-brain barrier. We present an integrated multimodal imaging biohybrid, GV@pCY5, which enables blood-brain barrier penetrating as well as fluorescence and ultrasound (FL/US) imaging capabilities. This biohybrid is created by decorating a far-red-fluorescent cyanine dye (CY5) onto polyethyleneimine (PEI)-coated gas vesicles (GV). The layer-by-layer assembly improves the stability and performance of GV@pCY5 under ultrasound, thanks to the hydration shell variation induced by PEI. Given to the blood-brain barrier penetrating ability, GV@pCY5 demonstrates increase both in fluorescence and ultrasound imaging performance compared to single-component systems, proving effective for glioma diagnosis in vivo. This study underscores the potential of the FL/US platform for dual ratiometric imaging of various cerebral conditions.