Endocytosis of Particle Formulations by Macrophages and Its Application to Clinical Treatment

Hirota, Keiji; Terada, Hiroshi

doi:10.5772/45820

Cited by 70 publications

(60 citation statements)

References 92 publications

(90 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This contradicts the observation that phagocytic cell lines favored the uptake of larger particles [70]. The highest attachment has been observed for particles with a longest dimension of 2 mm to 3 mm [118], which also represents the largest dimension of commonly found bacteria [80]. One possible explanation for such contradictions is "the difficulties in controlling the surface charge during the size control processes and the lack in surface functionality" [70].…”

Section: Cellular Uptake Of Nanoparticlesmentioning

confidence: 94%

Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type

Kettler

Veltman

Meent

et al. 2014

Enviro Toxic and Chemistry

348

210

View full text Add to dashboard Cite

The increased application of nanoparticles (NPs) is increasing the risk of their release into the environment. Although many toxicity studies have been conducted, the environmental risk is difficult to estimate, because uptake mechanisms are often not determined in toxicity studies. In the present study, the authors review dominant uptake mechanisms of NPs in cells, as well as the effect of NP properties, experimental conditions, and cell type on NP uptake. Knowledge of NP uptake is crucial for risk assessment and is essential to predict the behavior of NPs based on their physical-chemical properties. Important uptake mechanisms for eukaryotic cells are macropinocytosis, receptor-mediated endocytosis, and phagocytosis in specialized mammalian cells. The studies reviewed demonstrate that uptake into nonphagocytic cells depends strongly on NP size, with an uptake optimum at an NP diameter of approximately 50 nm. Increasing surface charges, either positive or negative, have been shown to increase particle uptake in comparison with uncharged NPs. Another important factor is the degree of (homo-) aggregation. Results regarding shape have been ambiguous. Difficulties in the production of NPs, with 1 property changed at a time, call for a full characterization of NP properties. Only then will it be possible to draw conclusions as to which property affected the uptake.

show abstract

Section: Cellular Uptake Of Nanoparticlesmentioning

confidence: 94%

Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type

Kettler

Veltman

Meent

et al. 2014

Enviro Toxic and Chemistry

348

210

View full text Add to dashboard Cite

show abstract

“…26 In addition, particle size is involved in the activation of the innate immune system because it is likely the primary factor that regulates endocytosis of phagocytes, including macrophages. 27 Therefore, this study investigated mice administered with OVA plus variously sized SPs (30, 100, and 1000 nm). The production of anti-OVA IgG antibodies and proliferative responses of splenocytes to OVA were enhanced in a size-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of ovalbumin-specific Th1, Th2, and Th17 immune responses by amorphous silica nanoparticles

Toda

Yoshino

2016

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

Nanomaterials present in cosmetics and food additives are used for industrial applications. However, their safety profile is unclear. Amorphous silica nanoparticles (nSPs) are a widely used nanomaterial and have been shown to induce inflammatory cytokines following intratracheal administration in mice. The current study investigated the adjuvant effect of nSP30 (nSP with a diameter of 33 nm) on T helper (Th)1, Th2, and Th17 immune responses as well as immunoglobulin (Ig) levels in mice. BALB/c mice were intraperitoneally administered ovalbumin (OVA) with or without varying doses and varying sizes of nSPs. The adjuvant effect of nSPs was investigated by measuring OVA-specific IgG antibodies in sera, OVA-specific proliferative responses of splenocytes, and the production of Th1, Th2, and Th17 cytokines. Aluminum hydroxide was used as a positive adjuvant control. Anti-OVA IgG production, splenocyte proliferative responses, and secretion of IFN-γ, IL-2, IL-4, IL-5, and IL-17 were increased significantly in mice receiving a combined injection of nSP30 (30 or 300 µg) with OVA compared with OVA alone or a combined injection with nSP30 (3 µg). The responses were nSP30 dose-dependent. When different sized nSPs were used (with 30, 100, and 1000 nm diameters), the responses to OVA were enhanced and were size-dependent. The smaller sized nSP particles had a greater adjuvant effect. nSPs appear to exert a size-dependent adjuvant effect for Th1, Th2, and Th17 immune responses. Understanding the mechanisms of nSP adjuvanticity might lead to the development of novel vaccine adjuvants and therapies for allergic diseases caused by environmental factors.

show abstract

“…Endocytic uptake into phagocytic cells has been classified as pinocytosis or phagocytosis (large particles > 250 nm) based on particle size, energy requirements, and morphologic attributes observed by electron microscopy. In the cells, these phagosomes (Ton et al 2007;Hirota 2012;Oh and Park 2014) and endosomes fuse with lysosomes where the ingested materials are recycled or degraded. Indigestible materials are exocytosed or remain within the lysosome forming residual bodies.…”

Section: Vacuolated Cell Types Phagocytic Cellsmentioning

confidence: 99%

PEGylated Biopharmaceuticals

et al. 2015

View full text Add to dashboard Cite

PEGylation (the covalent binding of one or more polyethylene glycol molecules to another molecule) is a technology frequently used to improve the half-life and other pharmaceutical or pharmacological properties of proteins, peptides, and aptamers. To date, 11 PEGylated biopharmaceuticals have been approved and there is indication that many more are in nonclinical or clinical development. Adverse effects seen with those in toxicology studies are mostly related to the active part of the drug molecule and not to polyethylene glycol (PEG). In 5 of the 11 approved and 10 of the 17 PEGylated biopharmaceuticals in a 2013 industry survey presented here, cellular vacuolation is histologically observed in toxicology studies in certain organs and tissues. No other effects attributed to PEG alone have been reported. Importantly, vacuolation, which occurs mainly in phagocytes, has not been linked with changes in organ function in these toxicology studies. This article was authored through collaborative efforts of industry toxicologists/nonclinical scientists to address the nonclinical safety of large PEG molecules (>10 kilo Dalton) in PEGylated biopharmaceuticals. The impact of the PEG molecule on overall nonclinical safety assessments of PEGylated biopharmaceuticals is discussed, and toxicological information from a 2013 industry survey on PEGylated biopharmaceuticals under development is summarized. Results will contribute to the database of toxicological information publicly available for PEG and PEGylated biopharmaceuticals.

show abstract

Endocytosis of Particle Formulations by Macrophages and Its Application to Clinical Treatment

Cited by 70 publications

References 92 publications

Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type

Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type

Enhancement of ovalbumin-specific Th1, Th2, and Th17 immune responses by amorphous silica nanoparticles

PEGylated Biopharmaceuticals

Contact Info

Product

Resources

About