Molecular ultrasound imaging of neutrophil membrane-derived biomimetic microbubbles for quantitative evaluation of hepatic ischemia-reperfusion injury.
Molecular ultrasound imaging of neutrophil membrane-derived biomimetic microbubbles for quantitative evaluation of hepatic ischemia-reperfusion injury.
复制标题
中性粒细胞膜衍生的仿生微泡的分子超声成像用于定量评估肝缺血再灌注损伤。
作者：
Zhang Z;Miao X;Yao W;Ren J;Chen C;Li X;Yang J;You Y;Lin Y;Yin T;Hei Z
理论基础：肝缺血再灌注损伤(HIRI)的早期诊断在原位肝移植中是至关重要的，HIRI是早期同种异体移植功能障碍或原发无功能的主要原因。然而，肝活检仍然是临床上评估HIRI的主要方法，尽管它有许多并发症和缺点，如出血和不准确。在此，我们的目标是开发一种无创、高精度和特异性的检测HIRI的方法。方法：采用自上而下和自下而上相结合的方法制备中性粒细胞仿生微泡。中性粒细胞膜与脂质体按规定的质量比通过超声作用混合。小瓶中的空气与全氟丙烷交换，然后将溶液机械振动形成MBneu。结果：在大鼠HIRI模型中，MBneu保留了中性粒细胞蛋白，优先靶向炎症的肝脏组织，并因其人工磷脂含量而表现出典型的脂质体MBS的物理化学性质。MBneu可以定量评估HIRI的严重程度，有助于HIRI的早期诊断和预后预测。此外，MBneu被证明是安全的，没有免疫原性。结论：我们用MBneu对HIRI进行了分子超声成像。这一新的合成策略可能会在未来应用于使用其他细胞类型的不同临床场景。
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.