Shaping bio-inspired nanotechnologies to target thrombosis for dual optical-magnetic resonance imaging.
Arterial and venous thrombosis are among the most common causes of death and hospitalization worldwide. Nanotechnology approaches hold great promise for molecular imaging and diagnosis as well as tissue-targeted delivery of therapeutics. In this study, we developed and investigated bioengineered nanoprobes for identifying thrombus formation; the design parameters of nanoparticle shape and surface chemistry, i.e. incorporation of fibrin-binding peptides CREKA and GPRPP, were investigated. Two nanoparticle platforms based on plant viruses were studied - icosahedral cowpea mosaic virus (CPMV) and elongated rod-shaped tobacco mosaic virus (TMV). These particles were loaded to carry contrast agents for dual-modality magnetic resonance (MR) and optical imaging, and both modalities demonstrated specificity of fibrin bindingin vitrowith the presence of targeting peptides. Preclinical studies in a carotid artery photochemical injury model of thrombosis confirmed thrombus homing of the nanoprobes, with the elongated TMV rods exhibiting significantly greater attachment to thrombi than icosahedral (sphere-like) CPMV. Whilein vitrostudies confirmed fibrin-specificity conferred by the peptide ligands,in vivostudies indicated the nanoparticle shape had the greatest contribution toward thrombus targeting, with no significant contribution from either targeting ligand. These results demonstrate that nanoparticle shape plays a critical role in particle deposition at the site of vascular injury. Shaping nanotechnologies opens the door for the development of novel targeted diagnostic and therapeutic strategies (i.e., theranostics) for arterial and venous thrombosis.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106.
Amy M
AM
Wen
Harrington Heart and Vascular Institute, Case Cardiovascular Research Institute, Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Yunmei
Y
Wang
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106.
Kai
K
Jiang
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
Greg C
GC
Hsu
Harrington Heart and Vascular Institute, Case Cardiovascular Research Institute, Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Huiyun
H
Gao
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106.
Karin L
KL
Lee
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106.
Alice C
AC
Yang
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106.
Xin
X
Yu
Harrington Heart and Vascular Institute, Case Cardiovascular Research Institute, Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Daniel I
DI
Simon
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106. ; Department of Radiology, Case Western Reserve University, Cleveland, OH 44106. ; Department of Materials Science and Engineering, Case Western Reserve University, Cleveland, OH 44106. ; Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH 44106.
Nicole F
NF
Steinmetz