Complementary targeting of liposomes to IL-1α and TNF-α activated endothelial cells via the transient expression of VCAM1 and E-selectin

Gunawan, Rico C.; Almeda, Dariela; Auguste, Debra T.

doi:10.1016/j.biomaterials.2011.08.093

Cited by 39 publications

(46 citation statements)

References 27 publications

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“…As previously reported, VCAM1 and E-selectin gene expression increases as a function of time when exposed to inflammatory cytokines, peaking at 6 h [13,38]. This corresponds to an increase in protein surface expression on activated ECs.…”

Section: Ec Surface Adhesionsupporting

confidence: 61%

“…In vitro endothelial cell (EC) overexpression of VCAM1, ICAM1, and E-selectin by cytokine activation is analogous to gene expression profiles observed in in vivo inflammation [11]. We synthesized liposomes that complement the molecular ratio of ICAM1:E-selectin or VCAM1:E-selectin expressed on cytokine-activated ECs [12,13]. Several papers have adopted a dual targeting strategy to improve their targeting results [14,15].…”

Section: Introductionmentioning

confidence: 78%

“…Liposome binding and uptake was evaluated in ECs with and without IL-1a activation to mimic an inflamed and healthy endothelium, respectively [12,13]. The mean fluorescence intensity (MFI) fold-over isotype values reported are the mean fluorescence intensity of antibody functionalized liposomes bound to ECs divided by the fluorescence intensity of IgG labeled liposomes bound to ECs.…”

Section: Liposome Binding and Uptakementioning

confidence: 99%

“…Liposomes were modified with aVCAM1 and aE-selectin antibodies at 1:0, 1:1, and 0:1 ratios with an average antibody density of 1000 molecules/mm 2 ; this is 85% lower than typical targeting vehicles [13,45]. Liposome binding and uptake was evaluated in ECs with and without IL-1a activation to mimic an inflamed and healthy endothelium, respectively [12,13].…”

Section: Liposome Binding and Uptakementioning

confidence: 99%

“…Liposomes were prepared by the extrusion method as described in our previous publication [13]. Briefly, a mixture of DOPC:N-dod-PE or DSPC:N-dod-PE (95:5, mol:mol) in chloroform was dried under a nitrogen stream.…”

Section: Liposome Preparationmentioning

confidence: 99%

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Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting

2015

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Section: Ec Surface Adhesionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 78%

Section: Liposome Binding and Uptakementioning

confidence: 99%

Section: Liposome Binding and Uptakementioning

confidence: 99%

Section: Liposome Preparationmentioning

confidence: 99%

See 3 more Smart Citations

Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting

2015

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Evaluation of receptor‐ligand mechanisms of dual‐targeted particles to an inflamed endothelium

Fromen

Fish

Zimmerman

et al. 2016

Bioengineering & Transla Med

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Vascular‐targeted carriers (VTCs) are designed as leukocyte mimics, decorated with ligands that target leukocyte adhesion molecules (LAMs) and facilitate adhesion to diseased endothelium. VTCs require different design considerations than other targeted particle therapies; adhesion of VTCs in regions with dynamic blood flow requires multiple ligand‐receptor (LR) pairs that provide particle adhesion and disease specificity. Despite the ultimate goal of leukocyte mimicry, the specificity of multiple LAM‐targeted VTCs remains poorly understood, especially in physiological environments. Here, we investigate particle binding to an inflamed mesentery via intravital microscopy using a series of particles with well‐controlled ligand properties. We find that the total number of sites of a single ligand can drive particle adhesion to the endothelium, however, combining ligands that target multiple LR pairs provides a more effective approach. Combining sites of sialyl Lewis A (sLeA) and anti‐intercellular adhesion molecule‐1 (aICAM), two adhesive molecules, resulted in ∼3–7‐fold increase of adherent particles at the endothelium over single‐ligand particles. At a constant total ligand density, a particle with a ratio of 75% sLeA: 25% aICAM resulted in more than 3‐fold increase over all over other ligand ratios tested in our in vivo model. Combined with in vivo and in silico data, we find the best dual‐ligand design of a particle is heavily dependent on the surface expression of the endothelial cells, producing superior adhesion with more particle ligand for the lesser‐expressed receptor. These results establish the importance of considering LR‐kinetics in intelligent VTC ligand design for future therapeutics.

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Precision engineering of targeted nanocarriers

Deci

Liu

Dinh³

et al. 2018

WIREs Nanomed Nanobiotechnol

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Since their introduction in 1980, the number of advanced targeted nanocarrier systems has grown considerably. Nanocarriers capable of targeting single receptors, multiple receptors, or multiple epitopes have all been used to enhance delivery efficiency and selectivity. Despite tremendous progress, preclinical studies and clinically translatable nanotechnology remain disconnected. The disconnect in targeting efficacy may stem from poorly-understood factors such as receptor clustering, spatial control of targeting ligands, ligand mobility, and ligand architecture. Further, the relationship between receptor distribution and ligand architecture remains elusive. Traditionally, targeted nanocarriers were engineered assuming a "static" target. However, it is becoming increasingly clear that receptor expression patterns change in response to external stimuli and disease progression. Here, we discuss how cutting-edge technologies will enable a better characterization of the spatiotemporal distribution of membrane receptors and their clustering. We further describe how this will enable the design of new nanocarriers that selectively target the site of disease. Ultimately, we explore how the precision engineering of targeted nanocarriers that adapt to receptor dynamics will have the potential to drive nanotechnology to the forefront of therapy and make targeted nanomedicine a clinical reality. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

show abstract

Complementary targeting of liposomes to IL-1α and TNF-α activated endothelial cells via the transient expression of VCAM1 and E-selectin

Cited by 39 publications

References 27 publications

Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting

Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting

Evaluation of receptor‐ligand mechanisms of dual‐targeted particles to an inflamed endothelium

Precision engineering of targeted nanocarriers

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