Surface Modification with Lactadherin Augments the Attachment of Sonazoid Microbubbles to Glycoprotein IIb/IIIa

  • Kentaro Otani
    Address correspondence to: Kentaro Otani, Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita Osaka 565-8565, Japan.
    Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
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  • Atsunori Kamiya
    Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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  • Takahiro Miyazaki
    Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
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  • Ayumi Koga
    Department of Cardiovascular Surgery, National Cerebral and Cardiovascular Center, Osaka, Japan
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  • Ayako Inatomi
    Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
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  • Mariko Harada-Shiba
    Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan

    Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
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      Arginine–glycine–aspartate (RGD)-carrying microbubbles (MBs) have been utilized as a specific contrast agent for glycoprotein IIb/IIIa (αIIbβ3 integrin)-expressing activated platelets in ultrasound molecular imaging. Recently, we found that surface modification with lactadherin provides the RGD motif on the surface of phosphatidylserine-containing clinically available MBs, Sonazoid. Here, we examined the potential of lactadherin-bearing Sonazoid MBs to be targeted MBs for glycoprotein IIb/IIIa using the custom-designed in vitro settings with recombinant αIIbβ3 integrin, activated platelets or erythrocyte-rich human clots. By modification of the surface with lactadherin, a large number of Sonazoid MBs were attached to the αIIbβ3 integrin-coated and platelet-immobilized plate. Additionally, the video intensity of clots after incubation with lactadherin-bearing Sonazoid MBs was significantly higher than that with unmodified Sonazoid MBs, implying the number of attached Sonazoid MBs was increased by the modification with lactadherin. Our results suggest that the lactadherin-bearing Sonazoid MBs have the potential to be thrombus-targeted MBs.

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