Engineered Biosynthetic Gas Vesicles for Dual-Modality Ultrasound/NIR-II Imaging.

Gas vesicles (GVs) are genetically encoded ultrasound contrast agents, but their applications are limited by poor tumor targeting and single-modality imaging. Here, we engineer RGD-displaying GVs and integrate a near-infrared II (NIR-II) fluorophore (CH1055) into the protein shell, generating the dual-modal nanoprobe CH1055@GVs-RGD. Genetic and chemical modifications preserve the inherent acoustic properties of GVs. In vitro, GVs-RGD show efficient uptake by U87 MG cells and 3D tumor spheroids. In vivo, intratumoral injection yields sustained ultrasound signals and peripheral NIR-II fluorescence, while intravenous administration provides prolonged ultrasound and fluorescence detection at the tumor site. Importantly, CH1055@GVs-RGD exhibits significantly enhanced tumor accumulation compared to nontargeted controls, confirming the RGD-mediated targeting. This genetically and chemically programmed nanoprobe represents a new class of targeted dual-modal ultrasound/NIR-II contrast agents for efficient and specific solid tumor imaging.