Polymeric particles conjugated with a ligand to VCAM‐1 exhibit selective, avid, and focal adhesion to sites of atherosclerosis

Deosarkar, Sudhir P.; Malgor, Ramiro; Fu, Jie; Kohn, Leonard D.; Goetz, Douglas J.

doi:10.1002/bit.21885

Cited by 33 publications

(18 citation statements)

References 37 publications

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“…When administered as an intravenous bolus, particles bound to ApoE -/-aortas in a 5 times higher amount when compared to wild type aortas with a selectivity for plaque regions, showing that the concept of targeted delivery can also be applied in the macro vasculature, where flow and adhesion dynamics differ significantly from those in the microvasculature. Closer inspection of the plaques showed that particles accumulated predominantly in the periphery of the plaques, which might be explained by higher focal VCAM-1 expression [56,57].…”

Section: Biodegradable Polymeric Particlesmentioning

confidence: 97%

Targeting Adhesion Molecules in Cardiovascular Disorders

Haverslag¹,

Pasterkamp²,

Hoefer

2008

CHDDT

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Cell adhesion molecules are ubiquitously expressed proteins playing a central role in controlling cell migration, proliferation, survival, and apoptosis. Besides their key function in physiological maintenance of tissue integrity, adhesion molecules play an eminent role in various pathological processes. In cardiovascular disorders, cell adhesion molecules are particularly involved in atherogenesis and atherosclerotic plaque progression. They also play a critical role in myocardial infarction and reperfusion damage and a minor role in valvular stenosis and cardiomyopathy. Their common denominator: An increased expression of adhesion molecules involved in leukocyte extravasation and accumulation. Leukocyte extravasation is a multistep process, mediated by several cell adhesion molecules including selectins (P-, E- and L-), integrins and members of the Ig superfamily (ICAM-1, VCAM-1). These molecules can be targeted for imaging purposes (e.g. to identify atherosclerotic plaques) or can serve as biomarkers for plaque destabilization. Furthermore, cell adhesion molecules can serve as drugable targets to prevent leukocyte extravasation where warranted to decrease inflammatory tissue damage (e.g. reperfusion injury). Current techniques involve blocking of binding sites, targeted drug delivery using liposomes and polymeric particles as carriers or imaging of inflammation sites using labeled cells or antibodies. This review focuses on the role of cell adhesion molecules in cardiovascular disease and the use of targeting adhesion molecules for imaging purposes and local drug delivery in cardiovascular medicine.

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Section: Biodegradable Polymeric Particlesmentioning

confidence: 97%

Targeting Adhesion Molecules in Cardiovascular Disorders

Haverslag¹,

Pasterkamp²,

Hoefer

2008

CHDDT

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“…10 Indeed, several molecular imaging applications of nanoparticle formulation targeted to VCAM-1 have been demonstrated, such as perfluorocarbons, 11,12 iron oxides, 13,14 polymers, 15 and quantum dots. 16 …”

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confidence: 99%

Dual-Modal Magnetic Resonance and Fluorescence Imaging of Atherosclerotic Plaques in Vivo Using VCAM-1 Targeted Tobacco Mosaic Virus

Bruckman¹,

Jiang²,

et al. 2014

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The underlying cause of major cardiovascular events, such as myocardial infarctions and strokes, is atherosclerosis. For accurate diagnosis of this inflammatory disease, molecular imaging is required. Toward this goal, we sought to develop a nanoparticle-based, high aspect ratio, molecularly targeted magnetic resonance MR imaging contrast agent. Specifically, we engineered the plant viral nanoparticle platform tobacco mosaic virus (TMV) to target vascular cell adhesion molecule (VCAM)-1, which is highly expressed on activated endothelial cells at atherosclerotic plaques. To achieve dual optical and MR imaging in an atherosclerotic ApoE−/− mouse model, TMV was modified to carry near-infrared dyes and chelated Gd ions. Our results indicate molecular targeting of atherosclerotic plaques. On the basis of the multivalency and multifunctionality, the targeted TMV-based MR probe increased the detection limit significantly; the injected dose of Gd ions could be further reduced by 3 orders of magnitude compared to the suggested clinical use, demonstrating the utility of targeted nanoparticle cargo delivery.

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“…In addition to VCAM-1, various adhesion molecules (e.g., ICAM-1, E-selectin, and PECAM-1) have been implicated in atherosclerosis. 20,26 The fact that VCAM-1 has been shown to play a critical role in atherosclerosis and is highly expressed at the sites of atherosclerosis 12,20,22,26 led us to select VCAM-1 as the marker of inflammation in atherosclerosis. Our working hypothesis is that the endothelial cells that detach from an inflamed vascular site in atherosclerosis would exhibit a distinct VCAM-1 expression profile, generally higher than normal.…”

Section: Discussionmentioning

confidence: 99%

“…To characterize the phenotype of the detected endothelial cells, we focused on vascular cell adhesion molecule-1 (VCAM-1) which has been extensively studied with regard to atherosclerosis development and progression. 10,12,20,22,26 Indeed, VCAM-1 has been shown to be highly expressed at sites of atherosclerosis 12,22 and its expression by the endothelial cells within the plaque regions has been suggested as an important characteristic of the atherosclerotic phenotype. 23 The increased expression of VCAM-1 within the plaque regions is mainly due to the pro-inflammatory cytokines produced during atherogenesis.…”

Section: Introductionmentioning

confidence: 99%

A Quantitative Real-Time PCR Approach for the Detection and Characterization of Endothelial Cells in Whole Blood

et al. 2011

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Pathological inflammation and endothelial dysfunction in atherosclerosis causes endothelial cell detachment from affected vasculature giving rise to circulating endothelial cells (CECs). A blood-based assay that can detect and characterize CECs in atherosclerosis could serve as a valuable diagnostic. Thus, we sought to develop a prototypic assay that detects and characterizes the inflammatory state of endothelial cells present in blood. For this purpose, we spiked resting and inflamed human umbilical vein endothelial cells (HUVEC) into separate samples of whole blood. RNA was harvested and analyzed via quantitative real-time PCR (qPCR) using melanoma cell adhesion molecule (MCAM), as an endothelial marker, and vascular cell adhesion molecule (VCAM-1), which is increased on inflamed endothelium. We found that MCAM mRNA levels correlated with the number of HUVEC spiked into the blood. VCAM-1 mRNA levels were elevated, and correlated with the number of HUVEC, in blood spiked with inflamed HUVEC but not in blood spiked with resting HUVEC. VCAM-1 and MCAM mRNA levels were converted into numerical indices that indicate the inflammatory state of the HUVEC. Combined, the blood spiking studies demonstrate that a VCAM-1/MCAM qPCR assay can successfully detect inflamed endothelial cells in whole blood thus providing proof-of-concept for a diagnostic based on a coupled-phenotypic qPCR assay.

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Polymeric particles conjugated with a ligand to VCAM‐1 exhibit selective, avid, and focal adhesion to sites of atherosclerosis

Cited by 33 publications

References 37 publications

Targeting Adhesion Molecules in Cardiovascular Disorders

Targeting Adhesion Molecules in Cardiovascular Disorders

Dual-Modal Magnetic Resonance and Fluorescence Imaging of Atherosclerotic Plaques in Vivo Using VCAM-1 Targeted Tobacco Mosaic Virus

A Quantitative Real-Time PCR Approach for the Detection and Characterization of Endothelial Cells in Whole Blood

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