Size of submicrometric and nanometric particles affect cellular uptake and biological activity of macrophages<i>in vitro</i>

Leclerc, Lara; Rima, Wael; Boudard, Delphine; Pourchez, Jérémie; Forest, Valérie; Bin, Valérie; Mowat, Pierre; Perriat, Pascal; Tillement, Olivier; Grosseau, Philippe; Bernache‐Assollant, Didier; Cottier, Michèle

doi:10.3109/08958378.2012.699984

Cited by 35 publications

(26 citation statements)

References 40 publications

(34 reference statements)

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“…Although further studies are clearly required to document the influence of Alhydrogel® agglomeration state on in vivo neurotoxic effects, such a finding would not be unprecedented in the field of particle toxicology since both cellular uptake and distribution in the body of other types of particles are influenced by the particle size (Buzea et al, 2007;Reddy et al, 2007;Landsiedel et al, 2012), and aggregation rate (Mühlfeld et al, 2008), two parameters that strongly determine particle toxicity (Bell et al, 2014;Leclerc et al, 2012;Nascarella and Calabrese, 2012;Mold et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity

et al. 2017

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Nonlinear dose-response of aluminium hydroxide adjuvant particles: selective low dose neurotoxicity.Toxicology http://dx.doi.org/10.1016/j.tox. 2016.11.018 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. An unusual neuro-toxicological pattern limited to a low dose of Alhydrogel ® was observed.Neurobehavioural changes, including decreased activity levels and altered anxiety-like behaviour, were observed compared to controls in animals exposed to 200 µg Al/kg but not at 400 and 800 µg Al/kg. Consistently, microglial number appeared increased in the ventral forebrain of the 200 µg Al/kg group. Cerebral Al levels were selectively increased in animals exposed to the lowest dose, while muscle granulomas had almost completely disappeared at 6 months in these animals.We conclude that Alhydrogel® injected at low dose in mouse muscle may selectively induce long-term Al cerebral accumulation and neurotoxic effects. To explain this unexpected result, an avenue that could be explored in the future relates to the adjuvant size since the injected suspensions corresponding to the lowest dose, but not to the highest doses, exclusively contained small agglomerates in the bacteria-size range known to favour capture and, presumably, transportation by monocyte-lineage cells. In any event, the view that Alhydrogel® neurotoxicity obeys "the dose makes the poison" rule of classical chemical toxicity appears overly simplistic.

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Section: Discussionmentioning

confidence: 99%

Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity

et al. 2017

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“…Because TEM measurement requires samples to be air-dried before analysis, particle sizes measured by TEM are always slightly smaller than those from DLS with samples suspended in solution. 26 Generally speaking, the particle size directly measured from the TEM images was in good agreement with the DLS measurements. The release of siRNA from siRNA-NP and siRNA-NP-Ab (loaded with 1.5 nmol Cy3-labeled siRNA) was evaluated in PBS (pH 7.4) for 15 days ( Figure 2C).…”

Section: ■ Resultsmentioning

confidence: 86%

Biodegradable Film for the Targeted Delivery of siRNA-Loaded Nanoparticles to Vaginal Immune Cells

Yang

2015

Mol. Pharmaceutics

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The goal of this study was to develop and characterize a novel intravaginal film platform for targeted delivery of small interfering RNA (siRNA)-loaded nanoparticles (NP) to dendritic cells as a potential gene therapy for the prevention of sexually transmitted human immunodeficiency virus (HIV) infection. Poly(ethylene glycol) (PEG)-functionalized poly(D, L-lactic-co-glycolic acid) (PLGA)/polyethylenimine (PEI)/siRNA NP (siRNA-NP) were fabricated using a modified emulsion-solvent evaporation method and characterized for particle size, zeta potential, encapsulation efficiency (EE), and siRNA release. siRNA-NP were decorated with anti-HLA-DR antibody (siRNA-NP-Ab) for targeting delivery to HLA-DR+ dendritic cells (DCs) and homogeneously dispersed in a biodegradable film consisting of poly vinyl alcohol (PVA) and λ-carrageenan. The siRNA-NP-Ab-loaded film (siRNA-NP-Ab-film) was transparent, displayed suitable physicomechanical properties, and was noncytotoxic. Targeting activity was evaluated in a mucosal coculture model consisting of a vaginal epithelial monolayer (VK2/E6E7 cells) and differentiated KG-1 cells (HLA-DR+ DCs). siRNA-NP-Ab were rapidly released from the film and were able to penetrate the epithelial layer to be taken up by differentiated KG-1 cells. siRNA-NP-Ab demonstrated higher targeting activity and significantly higher knockdown of synaptosome-associated 23-kDa protein (SNAP-23) mRNA and protein when compared to siRNA-NP without antibody conjugation. Overall, these data suggest that our novel siRNA-NP-Ab-film may be a promising platform for preventing HIV infection within the female genital tract.

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“…This previous work usually agrees with our data that smaller particles create an enhanced biological response. Typically, this previous work used engineered particles produced in laboratories at specific sizes, such as amorphous silica, titanium dioxide (TiO 2 ), or gold [18, 29, 35, 36]. Oberdorster et al observed significantly greater pulmonary inflammatory response to ultrafine (20-nm) TiO 2 in rats and mice when compared to larger particles (250-nm) [37].…”

Section: Discussionmentioning

confidence: 99%

“…Sager et al found that ultrafine (21-nm) TiO 2 particles caused significantly greater inflammation and were more cytotoxic than fine (1-μm) TiO 2 particles when instilled into rats [38]. Also, Leclerc et al investigated in vitro the rate of macrophage uptake and toxicity of fluorescent silica particles ranging from 850 to 150 nm and found that the smallest particles were internalized in greater quantities [18]. …”

Section: Discussionmentioning

confidence: 99%

“…Although occupational exposure to CS and the related health effects have been well documented in the scientific literature, many uncertainties still exist including the effect of the crystals’ surface characteristics, including particle size, on the development of disease [8, 13–18]. Most atmospheric studies suggest that the concentration of smaller particles correlates better with adverse health effects than the concentration of larger particles [16, 19–22]; however, there is little size-dependent toxicity data concerning CS.…”

Section: Introductionmentioning

confidence: 99%

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Differential activation of RAW 264.7 macrophages by size-segregated crystalline silica

Mischler

Cauda

Giuseppe

et al. 2016

J Occup Med Toxicol

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BackgroundOccupational exposure to crystalline silica is a well-established occupational hazard. Once in the lung, crystalline silica particles can result in the activation of alveolar macrophages (AM), potentially leading to silicosis, a fibrotic lung disease. Because the activation of alveolar macrophages is the beginning step in a complicated inflammatory cascade, it is necessary to define the particle characteristics resulting in this activation. The aim of this research was to determine the effect of the size of crystalline silica particles on the activation of macrophages.MethodsRAW 264.7 macrophages were exposed to four different sizes of crystalline silica and their activation was measured using electron microscopy, reactive oxygen species (ROS) generation by mitochondria, and cytokine expression.ResultsThese data identified differences in particle uptake and formation of subcellular organelles based on particle size. In addition, these data show that the smallest particles, with a geometric mean of 0.3 μm, significantly increase the generation of mitochondrial ROS and the expression of cytokines when compared to larger crystalline silica particles, with a geometric mean of 4.1 μm.ConclusionIn summary, this study presents novel data showing that crystalline silica particles with a geometric mean of 0.3 μm enhance the activation of AM when compared to larger silica particles usually represented in in vitro and in vivo research.

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Size of submicrometric and nanometric particles affect cellular uptake and biological activity of macrophagesin vitro

Cited by 35 publications

References 40 publications

Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity

Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity

Biodegradable Film for the Targeted Delivery of siRNA-Loaded Nanoparticles to Vaginal Immune Cells

Differential activation of RAW 264.7 macrophages by size-segregated crystalline silica

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