PEGylation of model drug carriers enhances phagocytosis by primary human neutrophils

Kelley, William M.; Fromen, Catherine A.; Lopez-Cazares, Genesis; Eniola‐Adefeso, Omolola

doi:10.1016/j.actbio.2018.09.001

Cited by 68 publications

(61 citation statements)

References 58 publications

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“…Some investigations support the inverse correlation between particle size and neutrophil uptake. Kelley et al [29] demonstrated the increased human neutrophil uptake following the size reduction of polystyrene nanoparticles. Gifford et al [30] suggested a facile uptake of iron oxide nanoparticles with a mean diameter of 110 nm by leukocytes.…”

Section: Discussionmentioning

confidence: 99%

Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

Liu

Umoro

et al. 2020

J Nanobiotechnol

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Background: Oleic acid (OA) is reported to show anti-inflammatory activity toward activated neutrophils. It is also an important material in nanoparticles for increased stability and cellular internalization. We aimed to evaluate the antiinflammatory activity of injectable OA-based nanoparticles for treating lung injury. Different sizes of nanocarriers were prepared to explore the effect of nanoparticulate size on inflammation inhibition. Results: The nanoparticles were fabricated with the mean diameters of 105, 153, and 225 nm. The nanocarriers were ingested by isolated human neutrophils during a 5-min period, with the smaller sizes exhibiting greater uptake. The size reduction led to the decrease of cell viability and the intracellular calcium level. The OA-loaded nanosystems dose-dependently suppressed the superoxide anion and elastase produced by the stimulated neutrophils. The inhibition level was comparable for the nanoparticles of different sizes. In the ex vivo biodistribution study, the pulmonary accumulation of nanoparticles increased following the increase of particle size. The nanocarriers were mainly excreted by the liver and bile clearance. Mice were exposed to intratracheal lipopolysaccharide (LPS) to induce acute respiratory distress syndrome (ARDS), like lung damage. The lipid-based nanocarriers mitigated myeloperoxidase (MPO) and cytokines more effectively as compared to OA solution. The larger nanoparticles displayed greater reduction on MPO, TNF-α, and IL-6 than the smaller ones. The histology confirmed the decreased pulmonary neutrophil recruitment and lung-architecture damage after intravenous administration of larger nanoparticles. Conclusions: Nanoparticulate size, an essential property governing the anti-inflammatory effect and lung-injury therapy, had different effects on activated neutrophil inhibition and in vivo therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

Liu

Umoro

et al. 2020

J Nanobiotechnol

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“…The attachment of poly(ethylene glycol) (PEG) onto the surface of nanoparticles is commonly thought to prevent particle opsonization and macrophage uptake. However, a recent study suggested, instead, that neutrophils preferentially internalized PEGylated particles (i.e., polystyrene microspheres) in the presence of human plasma 20 . Notably, when the authors used model cell lines such as HL-60 or THP-1 cultured in standard cell medium supplemented with 10% fetal bovine serum, PEGylation reduced uptake of the particles.…”

Section: Nanomaterials Effects On Neutrophilsmentioning

confidence: 97%

Nano-bio interactions: a neutrophil-centric view

et al. 2019

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Neutrophils are key components of the innate arm of the immune system and represent the frontline of host defense against intruding pathogens. However, neutrophils can also cause damage to the host. Nanomaterials are being developed for a multitude of different purposes and these minute materials may find their way into the body through deliberate or inadvertent exposure; understanding nanomaterial interactions with the immune system is therefore of critical importance. However, whereas numerous studies have focused on macrophages, less attention is devoted to nanomaterial interactions with neutrophils, the most abundant leukocytes in the blood. We discuss the impact of engineered nanomaterials on neutrophils and how neutrophils, in turn, may digest certain carbon-based materials such as carbon nanotubes and graphene oxide. We also discuss the role of the corona of proteins adsorbed onto the surface of nanomaterials and whether nanomaterials are sensed as pathogens by cells of the immune system.

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“…Furthermore, low PEG densities on nanoparticles resulted in rapid clearance of nanoparticles. Another study found that the addition of PEG to the surface of PS-COOH nanoparticle increased their uptake by neutrophils across multiple particles sizes of 2 µm, 500 nm, and 200 nm [24]. These studies also found no significant difference between the internalization of 200 nm PS-COOH nanoparticles [8].…”

Section: Discussionmentioning

confidence: 93%

Dense poly(ethylene glycol) coatings maximize nanoparticle transport across lymphatic endothelial cells and accumulate in the skindraining lymph nodes

McCright

Skeen

Yarmovsky

et al. 2020

Preprint

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Lymphatic vessels have received considerable attention in recent years as delivery route for immune modulatory therapies to the lymph nodes. Lymph node targeting of immunotherapies and vaccines has been shown to significantly enhance their therapeutic efficacy. Lymphatics transport functions materials from peripheral tissues to the lymph nodes, including small 10 – 250 nm therapeutic nanoparticles. While size required to enter lymphatic vessels, surface chemistry is more poorly studied. Here, we probed the effects of surface poly(ethylene glycol) (PEG) density on nanoparticle transport across lymphatic endothelial cells (LECs). We differentially PEGylated model carboxylate-modified polystyrene nanoparticles to form either a brush or dense brush PEG conformation on the nanoparticle surfaces. Using an established in-vitro lymphatic transport model, we found that the addition of any PEG improved the transport of nanoparticles through lymphatic endothelial cells (2.5 - 2.6 ± 0.9% transport efficiency at 24 hours) compared to the unmodified PS-COOH nanoparticles (0.05 ± 0.05% transport efficiency at 24 hours). Additionally, we found that transcellular transport is maximized (4.2 ± 0.7% transport efficiency at 24 hours) when the PEG is in a dense brush conformation on nanoparticle surfaces, corresponding with a high grafting density (Rf/D = 4.9). These results suggest that PEG conformation has a crucial role in determining translocation of nanoparticles across LECs and into lymphatic vessels. Thus, we identified PEG density as a major design criteria for maximizing lymphatic targeting of therapeutic nanoparticle formulations that can be widely applied to enhance immunotherapeutic and vaccine outcomes in future studies.

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PEGylation of model drug carriers enhances phagocytosis by primary human neutrophils

Cited by 68 publications

References 58 publications

Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

Nano-bio interactions: a neutrophil-centric view

Dense poly(ethylene glycol) coatings maximize nanoparticle transport across lymphatic endothelial cells and accumulate in the skindraining lymph nodes

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