Targeted nanocarriers for imaging and therapy of vascular inflammation

Chacko, Ann‐Marie; Hood, Elizabeth D.; Zern, Blaine J.; Muzykantov, Vladimir R.

doi:10.1016/j.cocis.2011.01.008

Cited by 68 publications

(73 citation statements)

References 90 publications

(112 reference statements)

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“…The effect of PEG molecular weight and surface density was examined using two receptor−ligand systems commonly explored for targeting endothelial inflammation; E-selectin/Sialyl Lewis a (sLe a ) and intercellular adhesion molecule-1 (ICAM-1)/anti-intercellular adhesion molecule-1 (aICAM-1). 19 Our results show that PEG spacers improved, diminished, or did not affect the adhesion efficacy of VTCs in blood depending on the PEG size and surface density, and the nature of the specific receptor−ligand kinetics employed.…”

Section: ■ Introductionmentioning

confidence: 88%

Effect of PEGylation on Ligand-Based Targeting of Drug Carriers to the Vascular Wall in Blood Flow

Onyskiw

Eniola‐Adefeso

2013

Langmuir

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The blood vessel wall plays a prominent role in the development of many life-threatening diseases and as such is an attractive target for treatment. To target diseased tissue, particulate drug carriers often have their surfaces modified with antibodies or epitopes specific to vascular wall-expressed molecules, along with poly(ethylene glycol) (PEG) to improve carrier blood circulation time. However, little is known about the effect of poly(ethylene glycol) on carrier adhesion dynamics-specifically in blood flow. Here we examine the influence of different molecular weight PEG spacers on particle adhesion in blood flow. Anti-ICAM-1 or Sialyl Lewis(a) were grafted onto polystyrene 2 μm and 500 nm spheres via PEG spacers and perfused in blood over activated endothelial cells at physiological shear conditions. PEG spacers were shown to improve, reduce, or have no effect on the binding density of targeted-carriers depending on the PEG surface conformation, shear rate, and targeting moiety.

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Section: ■ Introductionmentioning

confidence: 88%

Effect of PEGylation on Ligand-Based Targeting of Drug Carriers to the Vascular Wall in Blood Flow

Onyskiw

Eniola‐Adefeso

2013

Langmuir

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“…The dysfunctional endothelial cells impact leukocyte adhesion and recruitment, platelet activation, and thrombus formation 91, 94 . Endothelium-targeted nanoparticles in combination of medical imaging modalities including MRI, PET, and multiple-row detector computed tomography (MDCT) have been developed to visualize atherosclerotic endothelium wall structures and activities 39, 95 . Those nanoparticles can also prevent or treat atherosclerosis via targeted delivery of preventive or therapeutic agents to the activated or dysfunctional endothelial cells 94, 96 (Table 3).…”

Section: Nanoparticles Target Atherosclerotic Lesionsmentioning

confidence: 99%

“…VINP-28 also detected endothelial cells and other VCAM-1 expression cells in resected human carotid artery lesion ex vivo 101 . Other VCAM-1 ligands have been conjugated to nanoparticles for imaging endothelial cells 38, 39 . Beside VCAM-1, ICAM-1, selectins, stabilin-2, interleukine-4 receptor and other membrane proteins on activated or dysfunctional endothelial cells have been used as targets for designing endothelium-targeted nanoparticles 39, 103, 104 .…”

Section: Nanoparticles Target Atherosclerotic Lesionsmentioning

confidence: 99%

Detection and treatment of atherosclerosis using nanoparticles

Zhang

Dhanasekara

et al. 2016

WIREs Nanomed Nanobiotechnol

100

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Atherosclerosis is the key pathogenesis of cardiovascular disease, which is a silent killer and a leading cause of death in the United States. Atherosclerosis starts with the adhesion of inflammatory monocytes on the activated endothelial cells in response to inflammatory stimuli. These monocytes can further migrate into the intimal layer of the blood vessel where they are differentiate into macrophages, which take up oxidized low-density lipoproteins and release inflammatory factors to amplify the local inflammatory response. After accumulation of cholesterol, the lipid-laden macrophages are transformed into foam cells, the hallmark of the early stage of atherosclerosis. Foam cells can die from apoptosis or necrosis, the intracellular lipid is deposed in the artery wall forming lesions. The angiogenesis for nurturing cells is enhanced during lesion development. Proteases released from macrophages, foam cells and other cells degrade the fibrous cap of the lesion, resulting in rupture of the lesion and subsequent thrombus formation. Thrombi can block blood circulation, which represents a major cause of acute heart events and stroke. There are generally no symptoms in the early stages of atherosclerosis. Current detection techniques cannot easily, safely and effectively detect the lesions in the early stages, nor can they characterize the lesion feature such as the vulnerability. While the available therapeutic modalities cannot target specific molecules, cells, and processes in the lesions, nanoparticles appear to have a promising potential in improving atherosclerosis detection and treatment via targeting the intimal macrophages, foam cells, endothelial cells, angiogenesis, proteolysis, apoptosis, and thrombosis. Indeed, many nanoparticles have been developed in improving blood lipid profile and decreasing inflammatory response for enhancing therapeutic efficacy of drugs and decreasing their side effects.

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“…65 The family of CAMs are used for targeted delivery of drugs and imaging probes to the endothelium. 66,67 In this next section, we briefly review the in vitro flow models and their implementation with micro-and nanoparticles that have been specifically developed for: (1) studying the effect of disturbed flow on CAM expression and leukocyte recruitment and (2) evaluating the targeting efficiency to endothelium by using CAMs.…”

Section: Flow-based In Vitro Models and Cams Expressionmentioning

confidence: 99%

Targeting cell adhesion molecules with nanoparticles usingin vivoand flow-basedin vitromodels of atherosclerosis

Khodabandehlou

Masehi-Lano

Poon

et al. 2017

Exp Biol Med (Maywood)

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Impact statementAs atherosclerosis remains the leading cause of death, there is an urgent need to develop better tools for treatment of the disease. The ability to improve current treatments relies on enhancing the accuracy of in vitro and in vivo atherosclerotic models. While in vivo models provide all the relevant testing parameters, variability between animals and among models used is a barrier to reproducible results and comparability of NP efficacy. In vitro cultures isolate cells into microenvironments that fail to take into account flow separation and shear stress, which are characteristics of atherosclerotic lesions. Flow-based in vitro models provide more physiologically relevant platforms, bridging the gap between in vivo and 2D in vitro models. This is the first review that presents recent advances regarding endothelial cell-targeting using adhesion molecules in light of in vivo and flow-based in vitro models, providing insights for future development of optimal strategies against atherosclerosis. AbstractAtherosclerosis is a leading cause of death worldwide; in addition to lipid dysfunction, chronic arterial wall inflammation is a key component of atherosclerosis. Techniques that target cell adhesion molecules, which are overexpressed during inflammation, are effective methods to detect and treat atherosclerosis. Specifically, research groups have identified vascular cell adhesion molecule-1, intercellular adhesion molecule-1, platelet endothelial cell adhesion molecule, and selectins (E-selectin and P-selectin) as correlated to atherogenesis. In this review, we discuss recent strategies both in vivo and in vitro that target cell adhesion molecules. First, we discuss peptide-based and antibody (Ab)-based nanoparticles utilized in vivo for diagnostic, therapeutic, and theranostic applications. Second, we discuss flow-based in vitro models that serve to reduce the traditional disadvantages of in vivo studies such as variability, time to develop the disease, and ethical burden, but preserve physiological relevance. The knowledge gained from these targeting studies can be translated into clinical solutions for improved detection, prevention, and treatment of atherosclerosis.

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Targeted nanocarriers for imaging and therapy of vascular inflammation

Cited by 68 publications

References 90 publications

Effect of PEGylation on Ligand-Based Targeting of Drug Carriers to the Vascular Wall in Blood Flow

Effect of PEGylation on Ligand-Based Targeting of Drug Carriers to the Vascular Wall in Blood Flow

Detection and treatment of atherosclerosis using nanoparticles

Targeting cell adhesion molecules with nanoparticles usingin vivoand flow-basedin vitromodels of atherosclerosis

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