Targeting of nanoparticles to the clathrin-mediated endocytic pathway

Harush-Frenkel, Oshrat; Debotton, Nir; Benita, Simon; Altschuler, Yoram

doi:10.1016/j.bbrc.2006.11.135

Cited by 500 publications

(354 citation statements)

References 35 publications

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“…Studies using different NP charges have clearly shown that this factor influences both uptake mechanisms and down-stream immune outcomes. For instance, relative to anionic particles, cationic NPs appear to be taken up more readily via clathrin-mediated processes [21]. Furthermore, positively charged antigen-loaded NPs are significantly more effective at stimulating Th1 responses after either intradermal or mucosal (pulmonary) inoculation, whereas anionic particles stimulate T and B cell responses poorly under similar conditions [22,23].…”

Section: Chargementioning

confidence: 99%

Harnessing Nanoparticles for Immune Modulation

Getts¹,

Shea²,

Miller³

et al. 2016

Trends in Immunology

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Recent approaches using nanoparticles engineered for immune regulation have yielded promising results in preclinical models of disease. The number of nanoparticle therapies is growing, fueled by innovations in nanotechnology and advances in understanding of the underlying pathogenesis of immune-mediated diseases. In particular, recent mechanistic insight into the ways in which nanoparticles interact with the mononuclear phagocyte system and impact its function during homeostasis and inflammation have highlighted the potential of nanoparticle-based therapies for controlling severe inflammation while concurrently restoring peripheral immune tolerance in autoimmune disease. Here we review recent advances in nanoparticle-based approaches aimed at immune-modulation, and discuss these in the context of concepts in polymeric nanoparticle development, including particle modification, delivery and the factors associated with successful clinical deployment.

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Section: Chargementioning

confidence: 99%

Harnessing Nanoparticles for Immune Modulation

Getts¹,

Shea²,

Miller³

et al. 2016

Trends in Immunology

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“…Assembly of the triskelion leads to formation of a net-like basket (clathrin-coated pit) at the cell plasma membrane. Involvement of clathrin-mediated endocytosis in uptake/translocation of various nanoparticles in cells and tissues, eg, amidine-modified polystyrene nanoparticles in MDCK-II, 32 PEGylated D,L-polylactide (PLA) (PEG-PLA) nanoparticles into HeLa cells 49 and fullerenic nanoparticles into rat fibroblasts and rat hepatoma cells, 50 has been reported. Chlorpromazine and other inhibitors of clathrin-mediated endocytosis cause clathrin and AP-2 adaptor protein to relocate to multivesicular bodies and as a result inhibit clathrin-mediated endocytosis.…”

Section: Discussionmentioning

confidence: 99%

Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers

Fazlollahi¹,

Sipos²,

Kim³

et al. 2011

IJN

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Background: In this study, primary rat alveolar epithelial cell monolayers (RAECM) were used to investigate transalveolar epithelial quantum dot trafficking rates and underlying transport mechanisms. Methods: Trafficking rates of quantum dots (PEGylated CdSe/ZnS, core size 5.3 nm, hydrodynamic size 25 nm) in the apical-to-basolateral direction across RAECM were determined. Changes in bioelectric properties (ie, transmonolayer resistance and equivalent active ion transport rate) of RAECM in the presence or absence of quantum dots were measured. Involvement of endocytic pathways in quantum dot trafficking across RAECM was assessed using specific inhibitors (eg, methyl-β-cyclodextrin, chlorpromazine, and dynasore for caveolin-, clathrin-, and dynamin-mediated endocytosis, respectively). The effects of lowering tight junctional resistance on quantum dot trafficking were determined by depleting Ca 2+ in apical and basolateral bathing fluids of RAECM using 2 mM EGTA. Effects of temperature on quantum dot trafficking were studied by lowering temperature from 37°C to 4°C. Results: Apical exposure of RAECM to quantum dots did not elicit changes in transmonolayer resistance or ion transport rate for up to 24 hours; quantum dot trafficking rates were not surface charge-dependent; methyl-β-cyclodextrin, chlorpromazine, and dynasore did not decrease quantum dot trafficking rates; lowering of temperature decreased transmonolayer resistance by approximately 90% with a concomitant increase in quantum dot trafficking by about 80%; and 24 hours of treatment of RAECM with EGTA decreased transmonolayer resistance by about 95%, with increased quantum dot trafficking of up to approximately 130%. Conclusion: These data indicate that quantum dots do not injure RAECM and that quantum dot trafficking does not appear to take place via endocytic pathways involving caveolin, clathrin, or dynamin. We conclude that quantum dot translocation across RAECM takes place via both transcellular and paracellular pathways and, based on comparison with our prior studies, interactions of nanoparticles with RAECM are strongly dependent on nanoparticle composition and surface properties.

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“…Review Qu, He, Lin et al [42] Qaddoumi et al Endocytosis (CME) [113] Harush-Frenkel Endocytosis (CME) [114] Dausend et al Endocytosis (CvME) [116] Huang et al Endocytosis (CME) [118] Brown et al [63]. Numerical simula tions have also revealed that the minimum driv ing forces for NMs to penetrate the membrane depend on the NM shape (e.g., sphere, ellipsoids, rods, discs and pushpinlike) [64].…”

Section: Future Science Groupmentioning

confidence: 99%

Advances in The Understanding of Nanomaterial–Biomembrane Interactions and Their Mathematical and Numerical Modeling

Lin

et al. 2013

Nanomedicine

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The widespread application of nanomaterials (NMs), which has accompanied advances in nanotechnology, has increased their chances of entering an organism, for example, via the respiratory system, skin absorption or intravenous injection. Although accumulating experimental evidence has indicated the important role of NM–biomembrane interaction in these processes, the underlying mechanisms remain unclear. Computational techniques, as an alternative to experimental efforts, are effective tools to simulate complicated biological behaviors. Computer simulations can investigate NM–biomembrane interactions at the nanoscale, providing fundamental insights into dynamic processes that are challenging to experimental observation. This paper reviews the current understanding of NM–biomembrane interactions, and existing mathematical and numerical modeling methods. We highlight the advantages and limitations of each method, and also discuss the future perspectives in this field. Better understanding of NM–biomembrane interactions can benefit various fields, including nanomedicine and diagnosis.

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Targeting of nanoparticles to the clathrin-mediated endocytic pathway

Cited by 500 publications

References 35 publications

Harnessing Nanoparticles for Immune Modulation

Harnessing Nanoparticles for Immune Modulation

Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers

Advances in The Understanding of Nanomaterial–Biomembrane Interactions and Their Mathematical and Numerical Modeling

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