Action of polystyrene nanoparticles of different sizes on lysosomal function and integrity

Frőhlich, Eleonore; Meindl, Claudia; Roblegg, Eva; Ebner, Birgit; Absenger, Markus; Pieber, Thomas R.

doi:10.1186/1743-8977-9-26

Cited by 88 publications

(69 citation statements)

References 55 publications

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“…It should be noted that both for polystyrene beads and pDNA/PEI nanoparticles, the size and charge can change significantly in cell culture medium or optiMEM® (20 The basal expression levels of non-injected cells expressing GFP-LAMP1 and GFP-LC3 can be found in supplementary information (Suppl. Fig.…”

Section: Polystyrene Beads and Pdna/pei Polyplexesmentioning

confidence: 99%

Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: An additional barrier to non viral gene delivery

Remaut

Oorschot²,

Braeckmans

et al. 2014

Journal of Controlled Release

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Autophagy or 'self-eating' is a process by which defective organelles and foreign material can be cleared from the cell's cytoplasm and delivered to the lysosomes in which degradation occurs. It remains an open question, however, whether nanoparticles that did not enter the cell through endocytosis can also be captured from the cytoplasm by autophagy. We demonstrate that nanoparticles that are introduced directly in the cytoplasm of the cells by microinjection, can trigger an autophagy response. Moreover, both polystyrene beads and plasmid DNA containing poly-ethylene-imine complexes colocalize with autophagosomes and lysosomes, as was confirmed by electron microscopy.This indicates that cytoplasmic capturing of nanoparticles can occur by an autophagy response. The capturing of nanoparticles from the cytoplasm most likely limits the time frame in which efficient nucleic acid delivery can be obtained. Hence, autophagy forms an additional barrier to non-viral gene delivery, a notion that was not often taken into account before. Furthermore, these findings urges us to reconsider the idea that a single endosomal escape event is sufficient to have the long-lasting presence of nanoparticles in the cytoplasm of the cells.

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Section: Polystyrene Beads and Pdna/pei Polyplexesmentioning

confidence: 99%

Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: An additional barrier to non viral gene delivery

Remaut

Oorschot²,

Braeckmans

et al. 2014

Journal of Controlled Release

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“…It was first shown by several studies that since NPs are sequestered in lysosomes they could accumulate in those compartments and induce lysosomal dysfunction by inducing membrane permeability or defects in lysosomal trafficking. 27,29,54 We could show that particles were mainly localized in vesicles, including lysosomes, but not in other cellular compartments such as mitochondria or the cell nucleus.…”

mentioning

confidence: 88%

“…Following 16 hours incubation with 25 µg/mL PS particles, lysosomes were stained using the lysosomal marker LysoTracker ® Deep Red, which labels acidic organelles, 3,[27][28][29] and examined by confocal microscopy. While almost all 20 nm PS particles co-localized with lysosomes, fewer 1,000 nm PS particles co-localized in lysosomes ( Figure 7A, arrows).…”

mentioning

confidence: 99%

Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation

Seydoux¹,

Rothen‐Rutishauser²,

Nita³

et al. 2014

IJN

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Introduction Nanosized particles may enable therapeutic modulation of immune responses by targeting dendritic cell (DC) networks in accessible organs such as the lung. To date, however, the effects of nanoparticles on DC function and downstream immune responses remain poorly understood. Methods Bone marrow–derived DCs (BMDCs) were exposed in vitro to 20 or 1,000 nm polystyrene (PS) particles. Particle uptake kinetics, cell surface marker expression, soluble protein antigen uptake and degradation, as well as in vitro CD4 + T-cell proliferation and cytokine production were analyzed by flow cytometry. In addition, co-localization of particles within the lysosomal compartment, lysosomal permeability, and endoplasmic reticulum stress were analyzed. Results The frequency of PS particle–positive CD11c + /CD11b + BMDCs reached an early plateau after 20 minutes and was significantly higher for 20 nm than for 1,000 nm PS particles at all time-points analyzed. PS particles did not alter cell viability or modify expression of the surface markers CD11b, CD11c, MHC class II, CD40, and CD86. Although particle exposure did not modulate antigen uptake, 20 nm PS particles decreased the capacity of BMDCs to degrade soluble antigen, without affecting their ability to induce antigen-specific CD4 + T-cell proliferation. Co-localization studies between PS particles and lysosomes using laser scanning confocal microscopy detected a significantly higher frequency of co-localized 20 nm particles as compared with their 1,000 nm counterparts. Neither size of PS particle caused lysosomal leakage, expression of endoplasmic reticulum stress gene markers, or changes in cytokines profiles. Conclusion These data indicate that although supposedly inert PS nanoparticles did not induce DC activation or alteration in CD4 + T-cell stimulating capacity, 20 nm (but not 1,000 nm) PS particles may reduce antigen degradation through interference in the lysosomal compartment. These findings emphasize the importance of performing in-depth analysis of DC function when developing novel approaches for immune modulation with nanoparticles.

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“…In addition, we used larger beads (200 nm) to enable visualization in transmission electron microscopy. These beads are manufacture labeled with proprietary fluorescence dye; a recent study showed minimal dye leakage (<0.05% in 24-72 h; (14)). The molar concentration of NP was calculated using Eq.…”

Section: Polystyrene Beadsmentioning

confidence: 99%

Predictive Models of Diffusive Nanoparticle Transport in 3-Dimensional Tumor Cell Spheroids

Gao

Chen

et al. 2013

AAPS J

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Abstract. The rapidly evolving nanotechnology field highlights the need of better understanding the relationship between nanoparticle (NP) properties and NP transport in solid tumors. The present study tested the hypothesis that the diffusive transport and spatial distribution of NP can be predicted based on the following parameters: interstitial NP diffusivity, NP-cell interaction parameters (cell surface binding capacity, rate constants of association, dissociation, and internalization). We (a) established the models and equations; (b) experimentally measured, in monolayer pharynx FaDu cells, the model parameters for three NP formulations (negatively charged polystyrene beads, near-neutral liposomes, and positively charged liposomes, with respective diameter of 20, 110, and 130 nm); and (c) used the models and parameters to simulate NP diffusion in 3-dimensional (3D) systems. We next measured the NP concentration-depth profiles in tumor cell spheroids, an avascular 3D system, and found good agreement between model-simulated and experimental data in spheroids for the negative and neutral NP (>90% predicted data points at three NP concentrations and three treatment times were within the 95% confidence intervals of experimental data). Model performance was inferior for positive liposomes containing a fusogenic lipid. The present study demonstrated the possibility of using in vitro NP-cell biointerface data in monolayer cultures with in silico studies to predict the NP diffusive transport and concentration-time-depth profiles in 3D systems, as functions of NP concentrations and treatment times. Extending this approach to include convective transport may yield a cost-effective means to predict the NP delivery and residence in solid tumors.

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Action of polystyrene nanoparticles of different sizes on lysosomal function and integrity

Cited by 88 publications

References 55 publications

Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: An additional barrier to non viral gene delivery

Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: An additional barrier to non viral gene delivery

Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation

Predictive Models of Diffusive Nanoparticle Transport in 3-Dimensional Tumor Cell Spheroids

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