DSPC or DPPC as main shell component influences ligand distribution and binding area of lipid-coated targeted microbubbles
DSPC or DPPC as main shell component influences ligand distribution and binding area of lipid-coated targeted microbubbles
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DOI：
10.1002/ejlt.201300434
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发表时间：
2014-09-01
影响因子：
2.7
通讯作者：
de Jong, Nico
中科院分区：
文献类型：
--
作者：
Kooiman, Klazina;Kokhuis, Tom J. A.;de Jong, Nico
超声造影剂（UCA）由直径为1-10 μ m的充气涂层微泡组成。有针对性的UCA可以通过涂层结合配体与疾病相关的生物标志物结合，使超声分子成像成为可能。我们的研究的目的是使用超分辨率显微镜比较基于1，2-二硬脂酰-sn-甘油-3-磷酸胆碱（DSPC）和基于1，2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）的脂质涂层微泡的配体分布、结合面积和结合微泡形状。通过将荧光链霉亲和素俄勒冈州绿色488与生物素化的微泡缀合来研究配体分布。当DSPC为主要包被脂质时，发现链霉亲和素分布不均匀。当用DPPC代替DSPC时，观察到更均匀的链霉亲和素分布。使用结合到链霉亲和素包被的表面的生物素化微泡研究靶向微泡的结合面积。DSPC微泡的结合面积明显小于DPPC微泡。结合的DSPC微泡保持球形，而DPPC微泡为圆顶形。这项研究表明，脂质包被的微泡在配体分布，结合面积，结合微泡形状的基础上，其主要的脂质成分不同。
Ultrasound contrast agents (UCA) consist of gas-filled coated microbubbles with diameters of 1-10 mu m. Targeted UCA can bind to biomarkers associated with disease through coating-incorporated ligands, making ultrasound molecular imaging possible. The aim of our research was to compare the ligand distribution, binding area, and bound microbubble shape of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) based and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) based lipid-coated microbubbles using super-resolution microscopy. Ligand distribution was studied by conjugating the fluorescent streptavidin Oregon Green 488 to the biotinylated microbubbles. An inhomogeneous streptavidin distribution was found when DSPC was the main coating lipid. When DSPC was replaced by DPPC, a more homogeneous streptavidin distribution was observed. Binding area of targeted microbubbles was studied using biotinylated microbubbles bound to a streptavidin-coated surface. DSPC microbubbles had a significantly smaller binding area than DPPC microbubbles. Whereas the bound DSPC microbubbles remained spherical, the DPPC microbubbles were dome-shaped. This study reveals that lipid-coated microbubbles differ in ligand distribution, binding area, and bound microbubble shape solely on the basis of their main lipid component.