Modification of PEG reduces the immunogenicity of biosynthetic gas vesicles

Yuanyuan Wang; Meijun Fu; Yaozhang Yang; Jinghan Zhang; Zhaomeng Zhang; Jingling Xiao; Yingjie Zhou; Fei Yan

doi:10.3389/fbioe.2023.1128268

Modification of PEG reduces the immunogenicity of biosynthetic gas vesicles

Front Bioeng Biotechnol. 2023 Mar 6:11:1128268. doi: 10.3389/fbioe.2023.1128268. eCollection 2023.

Authors

Yuanyuan Wang^{1

2}, Meijun Fu^{1

3}, Yaozhang Yang¹, Jinghan Zhang⁴, Zhaomeng Zhang², Jingling Xiao², Yingjie Zhou², Fei Yan^{1

3}

Affiliations

¹ CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
² NHC Key Laboratory of Family Planning and Healthy, Hebei Key Laboratory of Reproductive Medicine, Hebei Reproductive Hospital, Hebei Institute of reproductive health science and technology, Shijiazhuang, China.
³ University of Chinese Academy of Sciences, Beijing, China.
⁴ Department of Ultrasonography, Capital Medical University Affiliated Beijing Anzhen Hospoital, Beijing, China.

Abstract

Nanobubbles have received great attention in ultrasound molecular imaging due to their capability to pass through the vasculature and reach extravascular tissues. Recently, gas vesicles (GVs) from archaea have been reported as acoustic contrast agents, showing great potential for ultrasound molecular imaging. However, the immunogenicity and biosafety of GVs has not yet been investigated. In this study, we examined the immune responses and biosafety of biosynthetic GVs and polyethylene glycol (PEG)-modified GVs (PEG-GVs) in vivo and in vitro. Our findings suggest that the plain GVs showed significantly stronger immunogenic response than PEG-GVs. Less macrophage clearance rate of the RES and longer circulation time were also found for PEG-GVs, thereby producing the better contrast imaging effect in vivo. Thus, our study demonstrated the PEG modification of biosynthetic GVs from Halobacterium NRC-1 is helpful for the future application of GVs in molecular imaging and treatment.

Keywords: biosafety; gas vesicles; immunization; tumor imaging; ultrasound contrast agents.