Stromal cell-derived factor-1-targeted ultrasound contrast agent tightly binds to vascular endothelial cells

doi:10.3969/j.issn.2095-4344.2015.20.014

Abstract

Abstract:

BACKGROUND: Stromal cell-derived factor-1 (SDF-1) is one of the most powerful chemokines in myocardial infarction region and plays a particularly pivotal role in the homing of stem cells to an injured myocardium and promoting angiogenesis. On the other hand the microbubble and acoustics active substances carrying targetable ligands can be prepared into targeted ultrasound contrast agents that can be combined with living cells used for molecular imaging. The key of ultrasonic molecular imaging is to find “imaging targets”, and to successfully prepare targeted ultrasound contrast agent which can be combined with the imaging target specifically and efficiently.
OBJECTIVE: To prepare and evaluate targeted microbubble contrast agents with SDF-1 monoclonal antibody.
METHODS: Targeted microbubble contrast agent with SDF-1 monoclonal antibody was prepared using the
biotin-streptavidin method. The physiochemical properties of targeted microbubble contrast agent were evaluated by appearance, pH, particle diameter, optical and fluorescence microscope and flow cytometry test. Four minipigs underwent ligation of the left anterior descending coronary artery to complete the establishment of acute myocardial infarction model, and another two minipigs were subject to thoracotomy but no ligation of the coronary artery. Then, all animals were injected with microbubble contrast agents. The stability of microbubbles was assessed by immunofluorescence test in vivo.
RESULTS AND CONCLUSION: SDF-1 and microbubbles were combined by biotin-streptavidin method. In vitro appearance of the contrast agent was translucent yellow or green, and stratified after standing. pH vaule was 7.02±0.12 for non-targeted contrast agent and 6.10±0.19 for targeted microbubble contrast agent. Under the fluorescence microscope, the distribution and size of targeted microbubbles were uniform, and the microbubbles were surrounded by bright and ring shaped green fluorescence that had no changes after highly shaking. The diameter of microbubbles was (2 422.62±238.82) nm after carrying the SDF-1 antibody. Flow cytometry results showed that the carrying rate of targeted contrast agents was stable in different periods. In vivo test showed that targeted microbubbles gathered in vascular endothelial cell surface after acute myocardial infarction. These findings indicate that the targeted microbubble contrast agent carrying SDF-1 monoclonal antibody prepared by biotin-streptavidin method can be combined with vascular endothelial cells, and the binding rate is high and stable in vitro.

Key words: Tissue Engineering, Ultrasonography, Extracellular Gene

CLC Number:

R318

Wang Meng, Shi Qi, Mu Yu-ming, Tuerxunnayi Adi. Stromal cell-derived factor-1-targeted ultrasound contrast agent tightly binds to vascular endothelial cells[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(20): 3188-3194.

Figures/Tables 3

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