Mimicking the transit of nanoparticles through the body: when the path determines properties at the destination

Uskoković, Vuk; Wu, Victoria

doi:10.1007/s11051-020-04892-w

Cited by 6 publications

(6 citation statements)

References 80 publications

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“…At the same time, however, the corona composed of constitutive ions, Posner's clusters and similar metastable species and resembling the tail of a comet should be more prominent in ACP and more disruptive to the cell membrane and peptidoglycan assemblies sustaining its integrity compared to HAp (figure 13). Here it should be noted that this is a different, harder type of corona compared to the one originating from proteins present in the broth or another biological medium and forming copiously around CP nanoparticles [108]. Unlike this harder corona composed of ultrafine solid clusters, the soft, protein corona diminishes any toxicity associated with the membrane damage at the site of the nanoparticle contact with the cell [109].…”

Section: Discussionmentioning

confidence: 98%

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: mechanism of action

Tang

Uskoković

2020

Biomed. Mater.

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This is the final report of the study aimed at assessing the antimicrobial activity of calcium phosphate (CP) nanoparticles delivered in the form of hydroxyapatite (HAp) or amorphous CP (ACP) and understanding the fundamental principles behind their mechanisms of action. Not responding to propidium iodide and causing no gross morphological changes except moderate stress-induced filamentation in Escherichia coli (E. coli), CP nanoparticles were shown to be bacteriostatic, not bactericidal. Also, the lack of expression of genes involved in DNA repair indicated no genotoxic activity. In contrast, the softening of amide infrared bands and the partial dissociation of lipopolysaccharide structures comprising the membrane of Gram-negative Pseudomonas aeruginosa (P. aeruginosa) was detected in a vibrational spectroscopic analysis of the nanoparticle/bacterium interaction. Similarly, the inhibition of the growth of Staphylococcus aureus (S. aureus) was paralleled by a reduced integrated intensity and the softening of the C = O ester carbonyl stretch in lipoteichoic acid, a major component of the Gram-positive cell membrane. Electron microscopy analyses confirmed that changes to the cell membrane are a major mode of action of CP nanoparticles. While HAp got internalized by E. coli significantly more than ACP, the membrane damage was more pronounced in ACP-treated bacteria, which was explained by the higher surface reactivity of ACP. HAp nanoparticles decreased the activity of overexpressed efflux pumps in methicillin-resistant S. aureus, suggesting that they may hijack these pumps and use them to enter the cell without producing any visible damage to the membrane, thus acting on the cell from the inside out, as opposed to ACP, whose action is mostly external in mechanism. This may explain why HAp, unlike ACP, suppresses the mechanisms of resistance in methicillin- and multidrug-resistant S. aureus and P. aeruginosa, respectively. The findings of this study will be essential in the optimization of these nanoparticles for becoming an alternative to less biocompatible inorganics and small molecule antibiotics in the global effort to curb the rising resistance of bacterial pathogens to the existing therapies.

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Section: Discussionmentioning

confidence: 98%

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: mechanism of action

Tang

Uskoković

2020

Biomed. Mater.

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“…Namely, while Gram-negative species adhere onto the surface of HAp nanoparticles and as such become removed from the solution via centrifugation (if not being partially protected from lysis by mere adsorption onto nanoparticles that remain dispersed), there are competitive adsorption effects going on incessantly during the co-incubation period. These competitive dynamic effects may be largely analogous to the Vroman effect that protein adsorption is subject to [ 66 ]. In these scenarios, lighter and more motile bacteria would become initially adsorbed onto the particles but only to be replaced in subsequent stages by the bulkier and less diffusive bacteria, sending the former bacteria back into the medium, where they would be adopting a more dispersed form than initially, being as such more susceptible to detection.…”

Section: Resultsmentioning

confidence: 99%

“…According to this effect, more mobile entities tend to reach a foreign surface first and adsorb on it, but only to be later displaced by the less mobile, if not also bulkier, entities, which have a greater thermodynamic affinity for binding. This is a universal principle that applies not only to macromolecules but also to smaller molecular groups [ 66 ].…”

Section: Resultsmentioning

confidence: 99%

Altering Microbiomes with Hydroxyapatite Nanoparticles: A Metagenomic Analysis

Uskoković

Wu²

2022

Materials

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Hydroxyapatite (HAp), the most abundant biological material among mammals, has been recently demonstrated to possess moderate antibacterial properties. Metagenomics provides a series of tools for analyzing the simultaneous interaction of materials with larger communities of microbes, which may aid in optimizing the antibacterial activity of a material such as HAp. Here, a microbiome intrinsic to the sample of sandy soil collected from the base of an African Natal plum (Carissa macrocarpa) shrub surrounding the children’s sandbox at the Arrowhead Park in Irvine, California was challenged with HAp nanoparticles and analyzed with next-generation sequencing for hypervariable 16S ribosomal DNA base pair homologies. HAp nanoparticles overwhelmingly reduced the presence of Gram-negative phyla, classes, orders, families, genera and species, and consequently elevated the relative presence of their Gram-positive counterparts. Thermodynamic, electrostatic and chemical bonding arguments were combined in a model proposed to explain this selective affinity. The ability of amphiphilic surface protrusions of lipoteichoic acid in Gram-positive bacteria and mycolic acid in mycobacteria to increase the dispersibility of the bacterial cells and assist in their resistance to capture by the solid phase is highlighted. Within the Gram-negative group, the variability of the distal, O-antigen portion of the membrane lipopolysaccharide was shown to be excessive and the variability of its proximal, lipid A portion insufficient to explain the selectivity based on chemical sequence arguments. Instead, flagella-driven motility proves to be a factor favoring the evasion of binding to HAp. HAp displayed a preference toward binding to less pathogenic bacteria than those causative of disease in humans, while taxa having a positive agricultural effect were largely captured by HAp, indicating an evolutionary advantage this may have given it as a biological material. The capacity to selectively sequester Gram-negative microorganisms and correspondingly alter the composition of the microbiome may open up a new avenue in environmental and biomedical applications of HAp.

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“…On the other hand, the composition of the exposure media, especially the protein content, could also affect the behavior of NPs such as aggregation, bioavailability, and respective toxicity [33]. Many different proteins present in biological tissues/media could form a protein corona around NPs that affects NPs' behavior and its transport into the cells [34]. The RPMI 1640 medium has been supplemented with FBS which contains mainly bovine serum albumin and a great variety of other proteins.…”

Section: Particle Aggregation and Iron Releasementioning

confidence: 99%

“…Many different proteins present in biological tissues/media could form a protein corona around NPs that affects NPs' behavior and its transport into the cells [34]. The RPMI 1640 medium has been supplemented with FBS which contains mainly bovine serum albumin and a great variety of other proteins.…”

Section: Particle Aggregation and Iron Releasementioning

confidence: 99%

In Vitro Study of the Toxicity Mechanisms of Nanoscale Zero-Valent Iron (nZVI) and Released Iron Ions Using Earthworm Cells

et al. 2020

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During the last two decades, nanomaterials based on nanoscale zero-valent iron (nZVI) have ranked among the most utilized remediation technologies for soil and groundwater cleanup. The high reduction capacity of elemental iron (Fe0) allows for the rapid and cost-efficient degradation or transformation of many organic and inorganic pollutants. Although worldwide real and pilot applications show promising results, the effects of nZVI on exposed living organisms are still not well explored. The majority of the recent studies examined toxicity to microbes and to a lesser extent to other organisms that could also be exposed to nZVI via nanoremediation applications. In this work, a novel approach using amoebocytes, the immune effector cells of the earthworm Eisenia andrei, was applied to study the toxicity mechanisms of nZVI. The toxicity of the dissolved iron released during exposure was studied to evaluate the effect of nZVI aging with regard to toxicity and to assess the true environmental risks. The impact of nZVI and associated iron ions was studied in vitro on the subcellular level using different toxicological approaches, such as short-term immunological responses and oxidative stress. The results revealed an increase in reactive oxygen species production following nZVI exposure, as well as a dose-dependent increase in lipid peroxidation. Programmed cell death (apoptosis) and necrosis were detected upon exposure to ferric and ferrous ions, although no lethal effects were observed at environmentally relevant nZVI concentrations. The decreased phagocytic activity further confirmed sublethal adverse effects, even after short-term exposure to ferric and ferrous iron. Detection of sublethal effects, including changes in oxidative stress-related markers such as reactive oxygen species and malondialdehyde production revealed that nZVI had minimal impacts on exposed earthworm cells. In comparison to other works, this study provides more details regarding the effects of the individual iron forms associated with nZVI aging and the cell toxicity effects on the specific earthworms’ immune cells that represent a suitable model for nanomaterial testing.

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Mimicking the transit of nanoparticles through the body: when the path determines properties at the destination

Cited by 6 publications

References 80 publications

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: mechanism of action

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: mechanism of action

Altering Microbiomes with Hydroxyapatite Nanoparticles: A Metagenomic Analysis

In Vitro Study of the Toxicity Mechanisms of Nanoscale Zero-Valent Iron (nZVI) and Released Iron Ions Using Earthworm Cells

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