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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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VHPKQHRGGSKGC-liquid perfluorocarbon nanoparticles

VCAM-1-targeted NPs
, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: April 1, 2010.

Chemical name:VHPKQHRGGSKGC-liquid perfluorocarbon nanoparticles
Abbreviated name:VCAM-1-targeted nanoparticles
Agent category:Peptide
Target:Vascular cell adhesion molecule-1 (VCAM-1)
Target category:Receptor
Method of detection:Magnetic resonance imaging (MRI)
Source of signal:19F
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about VCAM-1.



Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used to create images because of their abundance in water molecules, which comprise >80% of most soft tissues. The contrast of proton MRI images depends mainly on the density of nuclear (proton spins), the relaxation times of the nuclear magnetization (T1, longitudinal; T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the use of contrast agents. Most contrast agents affect the T1 and T2 relaxation of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (1). Cross-linked iron oxide (CLIO) and other iron oxide formulations affect T2 primarily and lead to a decreased signal.

Endothelial cells are important cells in inflammatory responses (2, 3). Bacterial lipopolysaccharide (LPS), virus, inflammation, and tissue injury increase tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and other cytokine and chemokine secretion. Leukocyte emigration from blood is dependent on their ability to roll along endothelial cell surfaces and subsequently adhere to endothelial cell surfaces. Inflammatory mediators and cytokines induce chemokine secretion from endothelial cells and other vascular cells and increase their expression of cell surface adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), integrins, and selectins. Chemokines are chemotactic toward leukocytes and toward sites of inflammation and tissue injury. The movements of leukocytes through endothelial junctions into the extravascular space are highly orchestrated through various interactions with different adhesion molecules on endothelial cells (4).

VCAM-1 is found in very low amounts on the cell surface of resting endothelial cells and other vascular cells, such as smooth muscle cells and fibroblasts (5-9). VCAM-1 binds to very late antigen-4 (VLA-4) integrin on the cell-surface of leukocytes. IL-1 and TNFα increase expression of VCAM-1 and other cell adhesion molecules on the vascular endothelial cells, which leads to leukocyte adhesion to the activated endothelium. Furthermore, VCAM-1 expression was also induced by oxidized low-density lipoproteins under atherogenic conditions (10). Over-expression of VCAM-1 by atherosclerotic lesions plays an important role in their progression towards vulnerable plaques, which may erode and rupture. CLIO nanoparticles targeted with anti-VCAM-1 antibody are being developed as a noninvasive agent for VCAM-1 expression in vascular endothelial cells during different stages of inflammation in atherosclerosis (11). A linear peptide (VHPKQHR) homologous to VLA-4 bound to and was internalized by VCAM-1-expressing cells (12, 13). VHPKQHRGGSKGC was synthesized and conjugated to liquid perfluorocarbon (PFC) nanoparticles to form VCAM-1-targeted nanoparticles (14). MR imaging was performed utilizing the multiple 19F moieties for quantification.



The synthesis of VCAM-1-targeted nanoparticles was described by Southworth et al. (14) Liquid PFC mixture comprised 20% (v/v) perfluoro-15-crown-5-ether (CE), 1.5% surfactant/lipid, 1.7% glycerine, and 0.135mol% rhodamine in water. N-[{w-[4-(p-maleimidophenyl)butanoyl]amino} poly(ethylene glycol)2000] 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (MPB-PEG-DSPE) and VHPKQHRGGSKGC were added to the PFC emulsions in 1:1 molar ratio (0.09mol%) under nitrogen at 37°C. The mixture was then sonicated and emulsified at 20,000 PSI for 4 min at 4°C. The maleimide group on MPB-PEG-DSPE reacted with the thiol group on the peptide to form a thioether linkage. The nanoparticles were ~353 nm in diameter as measured by laser light scattering. The peptide conjugation efficiency was 88% with 870 peptides per nanoparticle.

In Vitro Studies: Testing in Cells and Tissues


Southworth et al. (14) performed cell-binding assays with VCAM-1-targeted nanoparticles using murine endothelial 2F-2B cells with fluorescence microscopy. The cells were clearly visualized with VCAM-1-targeted nanoparticles but not with non-targeted nanoparticles. Ani-VCAM-1 antibody inhibited the binding of VCAM-1-targeted nanoparticles to the cells.

Animal Studies



Southworth et al. (14) performed ex vivo MR imaging (19F) at 11.7T with kidneys (n = 6) from ApoE-/- and wild-type mice injected with VCAM-1-targeted nanoparticles at 2 h after injection. The 19F signal in the ApoE-/- kidneys from mice injected with targeted nanoparticles was 3-fold greater than that observed in the wild-type kidneys from mice injected with targeted nanoparticles. There were 36.6 ± 8.8 x 108 targeted nanoparticles/g versus 9.3 ± 2.2 x 108 non-targeted nanoparticles/g in the ApoE-/- kidneys. On the other hand, the number of nanoparticles was similar in the wild-type kidneys (15.6 and 15.4 x 108/g, respectively). Histoimmunostaining showed that there was a 2-fold greater expression of VCAM-1 in the ApoE-/- kidneys than the wild-type kidneys. No blocking experiment was performed.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.

NIH Support

HL073646, CA119342, R01 HL078631-04


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