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Salvati, Anna
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Salvati, Anna
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Salvati, Anna
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Now showing 1 - 10 of 14
- PublicationTheoretical framework for nanoparticle uptake and accumulation kinetics in dividing cell populationsNano-sized objects interact with biological systems in fundamentally novel ways, thereby holding great promise for targeted drug delivery. It has also been suggested they could constitute a hitherto unseen hazard. Numerous experimental studies in the field are taking place. We consider that the nature of the interactions allows a more fundamental theoretical framework to be developed. In particular, we describe the intimate link that develops between nanoparticle uptake and cell population evolution. Explicit analytical results are given and the theory compared to experimental observations.
416Scopus© Citations 28 - PublicationBiomolecular coronas provide the biological identity of nanosized materials(Nature Publishing Group, 2012-12-05)
; ; ; The search for understanding the interactions of nanosized materials with living organisms is leading to the rapid development of key applications, including improved drug delivery by targeting nanoparticles, and resolution of the potential threat of nanotechnological devices to organisms and the environment. Unless they are specifically designed to avoid it, nanoparticles in contact with biological fluids are rapidly covered by a selected group of biomolecules to form a corona that interacts with biological systems. Here we review the basic concept of the nanoparticle corona and its structure and composition, and highlight how the properties of the corona may be linked to its biological impacts. We conclude with a critical assessment of the key problems that need to be resolved in the near future.2945Scopus© Citations 1972 - PublicationTime and Space Resolved Uptake Study of Silica Nanoparticles by Human Cells(Royal Society of Chemistry, 2011)
; ; ; ; ; A spatio-temporal mapping of the uptake of silica (SiO2) nanoparticles of different sizes by lung epithelial cells has been obtained. Based on high control of nanoparticle dispersion in cell media and cell exposure, one obtains reproducible and quantitative time-resolved data using a combination of flow cytometry, fluorescence and electron microscopies. We are thereby able to give a rather detailed account of the journey of SiO2 nanoparticles from the early events of uptake to their final sub-cellular localization.1273Scopus© Citations 194 - PublicationParacrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles(Royal Society of Chemistry, 2014-03)
; ; ; ; ; ; ; Nanoparticle properties, such as small size relative to large highly modifiable surface area, offer great promise for neuro-therapeutics and nanodiagnostics. A fundamental understanding and control of how nanoparticles interact with the blood-brain barrier (BBB) could enable major developments in nanomedical treatment of previously intractable neurological disorders, and help ensure that nanoparticles not intended to reach the brain do not cause adverse effects. Nanosafety is of utmost importance to this field. However, a distinct lack of knowledge exists regarding nanoparticle accumulation within the BBB and the biological effects this may induce on neighbouring cells of the Central Nervous System (CNS), particularly in the long-term. This study focussed on the exposure of an in vitro BBB model to model carboxylated polystyrene nanoparticles (PS COOH NPs), as these nanoparticles are well characterised for in vitro experimentation and have been reported as non-toxic in many biological settings. TEM imaging showed accumulation but not degradation of 100 nm PS COOH NPs within the lysosomes of the in vitro BBB over time. Cytokine secretion analysis from the in vitro BBB post 24 h 100 nm PS COOH NP exposure showed a low level of pro-inflammatory RANTES protein secretion compared to control. In contrast, 24 h exposure of the in vitro BBB endothelium to 100 nm PS COOH NPs in the presence of underlying astrocytes caused a significant increase in pro-survival signalling. In conclusion, the tantalising possibilities of nanomedicine must be balanced by cautious studies into the possible long-term toxicity caused by accumulation of known 'toxic' and 'non-toxic' nanoparticles, as general toxicity assays may be disguising significant signalling regulation during long-term accumulation.409Scopus© Citations 34 - PublicationEffects of the Presence or Absence of a Protein Corona on Silica Nanoparticle Uptake and Impact on Cells(ACS Publications, 2012-06-21)
; ; ; ; ; Nanoparticles enter cells through active processes, thanks to their capability of interacting with the cellular machinery. The protein layer (corona) that forms on their surface once nanoparticles are in contact with biological fluids, such as the cell serum, mediates the interactions with cells in situ. As a consequence of this, here we show that the same nanomaterial can lead to very different biological outcomes, when exposed to cells in the presence or absence of a preformed corona. In particular, silica nanoparticles exposed to cells in the absence of serum have a stronger adhesion to the cell membrane and higher internalization efficiency, in comparison to what is observed in medium containing serum, when a preformed corona is present on their surface. The different exposure conditions not only affect the uptake levels but also result in differences in the intracellular nanoparticle location and impact on cells. Interestingly, we also show that after only one hour of exposure, a corona of very different nature forms on the nanoparticles exposed to cells in the absence of serum. Evidence suggests that these different outcomes can all be connected to the different adhesion and surface properties in the two conditions.2353Scopus© Citations 834 - PublicationNanoparticle Adhesion to the Cell Membrane and Its effect on Nanoparticle Uptake Efficiency(American Chemical Society, 2013-01-09)
; ; ; ; ; The interactions between nanosized particles and living systems are commonly mediated by what adsorbs to the nanoparticle in the biological environment, its biomolecular corona, rather than the pristine surface. Here, we characterize the adhesion toward the cell membrane of nanoparticles of different material and size and study how this is modulated by the presence or absence of a corona on the nanoparticle surface. The results are corroborated with adsorption to simple model supported lipid bilayers using a quartz crystal microbalance. We conclude that the adsorption of proteins on the nanoparticle surface strongly reduces nanoparticle adhesion in comparison to what is observed for the bare material. Nanoparticle uptake is described as a two-step process, where the nanoparticles initially adhere to the cell membrane and subsequently are internalized by the cells via energy-dependent pathways. The lowered adhesion in the presence of proteins thereby causes a concomitant decrease in nanoparticle uptake efficiency. The presence of a biomolecular corona may confer specific interactions between the nanoparticle-corona complex and the cell surface including triggering of regulated cell uptake. An important effect of the corona is, however, a reduction in the purely unspecific interactions between the bare material and the cell membrane, which in itself disregarding specific interactions, causes a decrease in cellular uptake. We suggest that future nanoparticle-cell studies include, together with characterization of size, charge, and dispersion stability, an evaluation of the adhesion properties of the material to relevant membranes.1689Scopus© Citations 580 - PublicationImaging approach to mechanistic study of nanoparticle interactions with the blood-brain barrier(ACS, 2014-05-27)
; ; ; ; ; ; Understanding nanoparticle interactions with the central nervous system, in particular the blood-brain barrier, is key to advances in therapeutics, as well as assessing the safety of nanoparticles. Challenges in achieving insights have been significant, even for relatively simple models. Here we use a combination of live cell imaging and computational analysis to directly study nanoparticle translocation across a human in vitro blood-brain barrier model. This approach allows us to identify and avoid problems in more conventional inferential in vitro measurements by identifying the catalogue of events of barrier internalization and translocation as they occur. Potentially this approach opens up the window of applicability of in vitro models, thereby enabling in depth mechanistic studies in the future. Model nanoparticles are used to illustrate the method. For those, we find that translocation, though rare, appears to take place. On the other hand, barrier uptake is efficient, and since barrier export is small, there is significant accumulation within the barrier. © 2014 American Chemical Society.191Scopus© Citations 100 - PublicationLow Dose of Amino-Modified Nanoparticles Induces Cell Cycle Arrest(ACS Publications, 2013-08-13)
; ; ; ; ; The interaction of nanoscaled materials with biological systems is currently the focus of a fast-growing area of investigation. Though many nanoparticles interact with cells without acute toxic responses, amino-modified polystyrene nanoparticles are known to induce cell death. We have found that by lowering their dose, cell death remains low for several days while, interestingly, cell cycle progression is arrested. In this scenario, nanoparticle uptake, which we have recently shown to be affected by cell cycle progression, develops differently over time due to the absence of cell division. This suggests that the same nanoparticles can trigger different pathways depending on exposure conditions and the dose accumulated.489Scopus© Citations 77 - PublicationQuantitative assessment of the comparative nanoparticle-uptake efficiency of a range of cell lines(Wiley, 2011-12-02)
; ; ; ; Interest continues to grow in the possibility of understanding the mechanism(s) of nanoparticle-cell interactions. At present there is little knowledge, and essentially no understanding, of the relevant length and time scales for nanoparticle-intracellular entry, and localization within cells, and the cell-specificity of nanoparticle uptake and localisation. We have investigated here the effect of particle size on the in vitro intracellular uptake of model fluorescent carboxyl-modified polystyrene nanoparticles in various cell lines commonly used for uptake studies. A range of micro- and nanoparticles of defined sizes (40 nm to 2 μm)were incubated with a series of cell types, including HeLa and A549 epithelial cells, 1321N1 astrocytes, HCMEC D3 endothelial cells and murine RAW 264.7 macrophages. Techniques such as confocal microscopy and flow cytometry were used to study particle uptake and sub-cellular localisation, making significant efforts to ensure reproducibility in a semi-quantitative approach. The results indicated that internalization of (nano)particles is highly size dependent for all cell lines studied and that the kinetics of uptake for the same nanoparticle varies in the different cell types. Interestingly, even cells non specialized for phagocytosis were able to internalize the larger nanoparticles. Intracellular uptake of all sizes of (nano)particles was observed to be the highest in RAW 264.7 cells (a specialized phagocytic cell line) and the lowest in the HeLa cells. Results suggests that (nano)particle uptake might not follow commonly defined size limits for uptake processes and highlights the variability of uptake kinetics for the same material in different cell types. These conclusions have important implications for the assessment of the safety of nanomaterials and potential biomedical applications of nanoparticles.1883Scopus© Citations 197 - PublicationTransferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface(Nature Publishing Group, 2013-01-20)
; ; ; ; ; ; ; ; ; Nanoparticles have been proposed as carriers for drugs, genes and therapies to treat various diseases1, 2. Many strategies have been developed to target nanomaterials to specific or over-expressed receptors in diseased cells, and these typically involve functionalizing the surface of nanoparticles with proteins, antibodies or other biomolecules. Here, we show that the targeting ability of such functionalized nanoparticles may disappear when they are placed in a biological environment. Using transferrin-conjugated nanoparticles, we found that proteins in the media can shield transferrin from binding to both its targeted receptors on cells and soluble transferrin receptors. Although nanoparticles continue to enter cells, the targeting specificity of transferrin is lost. Our results suggest that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona3, 4 can ‘screen’ the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting.2342Scopus© Citations 1333