Theranostics 2021; 11(14):6922-6935. doi:10.7150/thno.57794

Research Paper

Molecular ultrasound imaging of neutrophil membrane-derived biomimetic microbubbles for quantitative evaluation of hepatic ischemia-reperfusion injury

Zheng Zhang1*, Xiaoyan Miao2*, Weifeng Yao1*, Jie Ren2, Chaojin Chen1, Xiang Li1, Jing Yang1, Yujia You2, Yuejun Lin2, Tinghui Yin2✉, Ziqing Hei1✉

1. Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
2. Department of Medical Ultrasonic, Laboratory of Novel Optoacoustic (Ultrasonic) imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
*These authors contributed equally to this work.

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Citation:
Zhang Z, Miao X, Yao W, Ren J, Chen C, Li X, Yang J, You Y, Lin Y, Yin T, Hei Z. Molecular ultrasound imaging of neutrophil membrane-derived biomimetic microbubbles for quantitative evaluation of hepatic ischemia-reperfusion injury. Theranostics 2021; 11(14):6922-6935. doi:10.7150/thno.57794. Available from https://www.thno.org/v11p6922.htm

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Abstract

Rationale: Early diagnosis of hepatic ischemia-reperfusion injury (HIRI), the major cause of early allograft dysfunction or primary non-function, is critical in orthotopic liver transplantation. However, liver biopsy is still the primary method for HIRI evaluation in clinical practice despite its numerous complications and shortcomings such as hemorrhage and inaccuracy. Herein, we aimed to develop a non-invasive, highly accurate, and specific method for detecting HIRI.

Methods: We developed a top-down and bottom-up strategy to fabricate neutrophil biomimetic microbubbles (MBneu). Neutrophil membrane was mixed with liposomes at a defined mass ratio by sonication. The air in the vial was exchanged with perfluoropropane, and then the solution was mechanically vibrated to form MBneu.

Results: MBneu retained the neutrophil proteins, preferentially targeted inflamed hepatic tissue in a rat model of HIRI, and demonstrated physicochemical properties typical of liposome-based MBs because of its artificial phospholipid content. With MBneu we can quantitively evaluate the severity of HIRI, which is helpful for early diagnosis and the prediction of outcome. In addition, MBneu was shown to be safe and showed no immunogenicity.

Conclusion: We demonstrated molecular ultrasound imaging of HIRI with MBneu. This new synthesis strategy may be applied to different clinical scenarios using other cell types in the future.

Keywords: biomimetic, microbubbles, molecular ultrasound imaging, neutrophil, hepatic ischemia-reperfusion injury