微气泡
化学
剪应力
生物物理学
动力学
单克隆抗体
乙二醇
链霉亲和素
超声波
生物素
材料科学
生物化学
抗体
生物
免疫学
复合材料
医学
物理
放射科
量子力学
有机化学
作者
Amol Takalkar,Alexander L. Klibanov,Joshua J. Rychak,Jonathan R. Lindner,Klaus Ley
标识
DOI:10.1016/j.jconrel.2004.03.002
摘要
This study was performed to assess the binding kinetics of a targeted microbubble contrast agent exposed to shear stress. An ultrasound contrast targeted to P-selectin was designed by conjugating monoclonal antibodies against murine P-selectin (RB40.34) to the lipid monolayer shell of the microbubble using poly(ethylene glycol)-biotin-streptavidin. The attachment and detachment of targeted microbubbles to P-selectin immobilized on a culture dish were assessed in a parallel-plate flow chamber. Targeted microbubbles (5 x 10(6) particles/ml) drawn through the flow chamber coated with P-selectin (109 sites/microm(2)) at a shear stress of 0.3 dyn/cm(2) accumulated at a rate of 565 mm(-2) min(-1). Attachment rates increased at higher plate surface densities of P-selectin, and microbubble detachment was reduced. Accumulation rate first increased with shear stress, reached a maximum at approximately 0.6 dyn/cm(2) and then decreased. Control experiments on a plate that lacked P-selectin, or was blocked with mAb RB40.34, resulted in minimal bubble attachment. Microbubble detachment was tested by ramping up shear stress at 30-s intervals. Half-maximal detachment was reached at 34 dyn/cm(2). Overall, accumulation and retention of targeted ultrasound contrast agents is possible under physiologic flow conditions and is strongly influenced by shear stress and surface density of the target receptor.
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