Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/82113
Title: Surface-modified GVs as nanosized contrast agents for molecular ultrasound imaging of tumor
Authors: Wang, G 
Song, L 
Hou, X 
Kala, S 
Wong, KF 
Tang, L 
Dai, Y
Sun, L 
Issue Date: 2020
Source: Biomaterials, 2020, v. 236, 119803
Abstract: Nanobubbles, as a kind of new ultrasound contrast agent (UCAs), have shown promise to penetrate tumor vasculature to allow for targeted imaging. However, their inherent physical instability is an ongoing concern that could weaken their imaging ability with ultrasound. Gas vesicles (GVs), which are genetically encoded, naturally stable nanostructures, have been developed as the first ultrasonic biomolecular reporters which showed strong contrast enhancement. However, further development of tumor imaging with GVs is limited by the quick clearance of GVs by the reticuloendothelial system (RES). Here, we developed PEGylated HA-GVs (PH-GVs) for in-tumor molecular ultrasound imaging by integrating polyethylene glycol (PEG) and hyaluronic acid (HA) in GV shells. PH-GVs were observed to accumulate around CD44-positive cells (SCC7) but not be internalized by macrophage cell line RAW 264.7. Green fluorescence from PH-GVs was found around cell nuclei in the tumor site after 6 h and the signal was sustained over 48 h following tail injection, demonstrating PH-GVs’ ability to escape the clearance from the RES and to penetrate tumor vasculature through enhanced permeability and retention (EPR) effects. Further, PH-GVs produced strong ultrasound contrast in the tumor site in vivo, with no obvious side-effects detected following intravenous injection. Thus, we demonstrate the potential of PH-GVs as novel, nanosized and targeted UCAs for efficient and specific molecular tumor imaging, paving the way for the application of GVs in precise and personalized medicine.
Keywords: Contrast agents
Gas vesicles
Molecular imaging
Tumor diagnosis
Ultrasound
Publisher: Elsevier
Journal: Biomaterials 
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2020.119803
Rights: © 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
The following publication Wang, G., Song, L., Hou, X., Kala, S., Wong, K. F., Tang, L., ... & Sun, L. (2020). Surface-modified GVs as nanosized contrast agents for molecular ultrasound imaging of tumor. Biomaterials, 236, 119803, is available at https://doi.org/10.1016/j.biomaterials.2020.119803
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