Feasibility of Lactadherin-Bearing Clinically Available Microbubbles as Ultrasound Contrast Agent for Angiogenesis
Feasibility of Lactadherin-Bearing Clinically Available Microbubbles as Ultrasound Contrast Agent for Angiogenesis
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DOI：
10.1007/s11307-013-0630-2
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发表时间：
2013-03
影响因子：
3.1
通讯作者：
Kentaro Otani;K. Yamahara
中科院分区：
文献类型：
--
作者：
Kentaro Otani;K. Yamahara
ObjectivesPhagocytosis of apoptotic cells is carried out through bridging of phosphatidylserine (PS)-expressing apoptotic cells and integrin αvβ3-expressing phagocytes with lactadherin. The objective of this study was to examine whether microbubbles targeted to integrin αvβ3 could be produced by conjugating a PS-containing clinically available ultrasound contrast agent with lactadherin.Materials and MethodsPS-containing perfluorobutane-filled microbubbles were incubated with R-phycoerythrin (PE)-labeled lactadherin, and the presence of PE-positive bubbles was examined by FACS analysis. Secondly, the attachment of lactadherin to integrin αvβ3-expressing cells (human umbilical vein endothelial cells (HUVEC)) was also examined by FACS analysis. Finally, the adhesion of PS-containing bubbles to HUVEC was examined using a parallel plate flow chamber. The number of adherent bubbles with or without the intermediation of lactadherin was compared.ResultsThe more lactadherin was added to the bubble suspension, the more PE-positive bubbles were detected. The size of bubbles was not increased even after conjugation with lactadherin (2.90 ± 0.04 vs. 2.81 ± 0.02 μm). Binding between lactadherin and HUVEC was also confirmed by FACS analysis. The parallel plate flow chamber study revealed that the number of PS-containing bubbles adherent to HUVEC was increased about five times by the intermediation of lactadherin (12.1 ± 6.0 to 58.7 ± 33.1 bubbles).ConclusionBecause integrin αvβ3 is well-known to play a key role in angiogenesis, the complex of PS-containing bubbles and lactadherin has feasibility as a clinically translatable targeted ultrasound contrast agent for angiogenesis.
