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

Kentaro Otani; Atsunori Kamiya; Takahiro Miyazaki; Ayumi Koga; Ayako Inatomi; Mariko Harada-Shiba

doi:10.1016/j.ultrasmedbio.2019.01.022

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

Ultrasound Med Biol. 2019 Jun;45(6):1455-1465. doi: 10.1016/j.ultrasmedbio.2019.01.022. Epub 2019 Mar 9.

Authors

Kentaro Otani¹, Atsunori Kamiya², Takahiro Miyazaki³, Ayumi Koga⁴, Ayako Inatomi⁵, Mariko Harada-Shiba⁶

Affiliations

¹ Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. Electronic address: otani@ncvc.go.jp.
² Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
³ Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
⁴ Department of Cardiovascular Surgery, National Cerebral and Cardiovascular Center, Osaka, Japan.
⁵ Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
⁶ 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.

PMID: 30857759
DOI: 10.1016/j.ultrasmedbio.2019.01.022

Abstract

Arginine-glycine-aspartate (RGD)-carrying microbubbles (MBs) have been utilized as a specific contrast agent for glycoprotein IIb/IIIa (α_IIbβ₃ 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 α_IIbβ₃ 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 α_IIbβ₃ 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.

Keywords: Glycoprotein IIb/IIIa; Microbubble; Platelets; Thrombus; Ultrasound molecular imaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Surface / pharmacology*
Contrast Media / pharmacokinetics*
Female
Ferric Compounds / pharmacokinetics*
Humans
Image Enhancement / methods*
Iron / pharmacokinetics*
Male
Microbubbles*
Milk Proteins / pharmacology*
Molecular Imaging / methods
Oxides / pharmacokinetics*
Reference Values
Ultrasonography / methods*

Substances

Antigens, Surface
Contrast Media
Ferric Compounds
MFGE8 protein, human
Milk Proteins
Oxides
Sonazoid
Iron