Acute and Chronic Shear Stress Differently Regulate Endothelial Internalization of Nanocarriers Targeted to Platelet-Endothelial Cell Adhesion Molecule-1

Han, Jing‐Yan; Zern, Blaine J.; Shuvaev, Vladimir V.; Davies, Peter F.; Muro, Silvia; Muzykantov, Vladimir R.

doi:10.1021/nn302687n

Cited by 105 publications

(132 citation statements)

References 69 publications

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“…Studying this complex interplay has been difficult in static cell cultures or in vivo. Although cell cultures are simple to use, they lack the contribution of fluid dynamics from the perspective of both particlecell interactions and adaption of cells in response to shear (53). In vivo systems, although of direct relevance, suffer from the complexity of use and interference from other factors, such as immune clearance and kidney filtration.…”

Section: Discussionmentioning

confidence: 99%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

591

507

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Vascular endothelium offers a variety of therapeutic targets for the treatment of cancer, cardiovascular diseases, inflammation, and oxidative stress. Significant research has been focused on developing agents to target the endothelium in diseased tissues. This includes identification of antibodies against adhesion molecules and neovascular expression markers or peptides discovered using phage display. Such targeting molecules also have been used to deliver nanoparticles to the endothelium of the diseased tissue. Here we report, based on in vitro and in vivo studies, that the specificity of endothelial targeting can be enhanced further by engineering the shape of ligand-displaying nanoparticles. In vitro studies performed using microfluidic systems that mimic the vasculature (synthetic microvascular networks) showed that rodshaped nanoparticles exhibit higher specific and lower nonspecific accumulation under flow at the target compared with their spherical counterparts. Mathematical modeling of particle-surface interactions suggests that the higher avidity and specificity of nanorods originate from the balance of polyvalent interactions that favor adhesion and entropic losses as well as shear-induced detachment that reduce binding. In vivo experiments in mice confirmed that shape-induced enhancement of vascular targeting is also observed under physiological conditions in lungs and brain for nanoparticles displaying anti-intracellular adhesion molecule 1 and anti-transferrin receptor antibodies.biodistribution | morphology | SMN | cylinder | drug delivery

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Section: Discussionmentioning

confidence: 99%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

591

507

View full text Add to dashboard Cite

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“…In particular, conjugating antioxidants or their carriers to ligands of the endothelial cell surface determinant Platelet Endothelial Cell Adhesion Molecule, PECAM-1, represents an attractive strategy [16, 17]. Anti-PECAM targeted conjugates bind to the endothelium and are internalized via the noncanonical CAM-mediated endocytic pathway [21-23]. Further, AOEs conjugated with anti-PECAM, but not with control IgG, have been shown to 1) enter endosomes in vitro and in vivo [22, 24, 25], 2) quench endothelial ROS [12, 22, 26], and 3) alleviate lung ischemia-reperfusion [18, 27], vascular oxidative stress [28], and angiotensin-induced vasoconstriction in vivo [27].…”

Section: Introductionmentioning

confidence: 99%

Endothelial targeting of liposomes encapsulating SOD/catalase mimetic EUK-134 alleviates acute pulmonary inflammation

Howard

Greineder

Hood

et al. 2014

Journal of Controlled Release

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Production of excessive levels of reactive oxygen species (ROS) in the vascular endothelium is a common pathogenic pathway in many dangerous conditions, including acute lung injury, ischemia-reperfusion, and inflammation. Ineffective delivery of antioxidants to the endothelium limits their utility for management of these conditions. In this study, we devised a novel translational antioxidant intervention targeted to the vascular endothelium using PEG-liposomes loaded with EUK-134 (EUK), a potent superoxide dismutase/catalase mimetic. EUK loaded into antibody-coated liposomes (size 197.8±4.5 nm diameter, PDI 0.179±0.066) exerted partial activity in the intact carrier, while full activity was recovered upon liposome disruption. For targeting we used antibodies (Abs) to platelet-endothelial cell adhesion molecule (PECAM-1). Both streptavidin-biotin and SATA/SMCC conjugation chemistries provided binding of 125-150 Ab molecules per liposome. Ab/EUK/liposomes, but not IgG/EUK/liposomes: i) bound to endothelial cells and inhibited cytokine-induced inflammatory activation in vitro; and, ii) accumulated in lungs after intravascular injection, providing >60% protection against pulmonary edema in endotoxin-challenged mice (vs <6% protection afforded by IgG/liposome/EUK counterpart). Since the design elements of this drug delivery system are already in clinical use (PEG-liposomes, antibodies, SATA/SMCC conjugation), it is an attractive candidate for translational interventions using antioxidant molecules such as EUK and other clinically acceptable drugs.

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“…32 These mechanisms now inspire targeted delivery strategies and cell capture schemes in the assessment of cancer treatment. 48−51 …”

Section: ■ Introductionmentioning

confidence: 99%

Nanoscale Functionalized Particles with Rotation-Controlled Capture in Shear Flow

Shave

Kalasin

Ying

et al. 2018

ACS Appl. Mater. Interfaces

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Important processes in nature and technology involve the adhesive capture of flowing particles or cells on the walls of a conduit. This paper introduces engineered spherical microparticles whose capture rates are limited by their near surface motions in flow. Specifically, these microparticles are sparsely functionalized with nanoscopic regions (“patches”) of adhesive functionality, without which they would be nonadhesive. Not only is particle capture on the wall of a shearchamber limited by surface chemistry as opposed to transport, but also the capture rates depend specifically on particle rotations that result from the vorticity of the shear flow field. These particle rotations continually expose new particle surface to the opposing chamber wall, sampling the particle surface for an adhesive region and controlling the capture rate. Control studies with the same patchy functionality on the chamber wall rather than the particles reveal a related signature of particle capture but substantially faster (still surface limited) particle capture rates. Thus, when the same functionality is placed on the wall rather than the particles, the capture is faster because it depends on the particle translation past a functionalized wall rather than on the particle rotations. The dependence of particle capture on functionalization of the particles versus the wall is consistent with the faster near-wall particle translation in shearing flow compared with the velocity of the rotating particle surface near the wall. These findings, in addition to providing a new class of nanoscopically patchy engineered particles, provide insight into the capture and detection of cells presenting sparse distinguishing surface features and the design of delivery packages for highly targeted pharmaceutical delivery.

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Acute and Chronic Shear Stress Differently Regulate Endothelial Internalization of Nanocarriers Targeted to Platelet-Endothelial Cell Adhesion Molecule-1

Cited by 105 publications

References 69 publications

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Endothelial targeting of liposomes encapsulating SOD/catalase mimetic EUK-134 alleviates acute pulmonary inflammation

Nanoscale Functionalized Particles with Rotation-Controlled Capture in Shear Flow

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