| 1. |
- Bhattacharya, Kunal, et al.
(author)
-
Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes
- 2014
-
In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 6:24, s. 14686-14690
-
Journal article (peer-reviewed)abstract
- Single-walled carbon nanotubes (SWCNTs) coated or functionalized with PEG chains of different molecular weight were assessed for their propensity to undergo biodegradation under in vitro conditions using recombinant myeloperoxidase (MPO) or ex vivo using freshly isolated primary human neutrophils. Our findings suggest that under natural conditions, a combined process of 'stripping' (i.e., defunctionalization) and biodegradation of PEG-SWCNTs might occur and that PEG-SWCNTs are a promising-and degradable-nanomedicine vector.
|
|
| 2. |
|
|
| 3. |
- Bhattacharya, Kunal, et al.
(author)
-
Nitric Oxide Dependent Degradation of Polyethylene Glycol-Modified Single-Walled Carbon Nanotubes : Implications for Intra-Articular Delivery
- 2018
-
In: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 7:6
-
Journal article (peer-reviewed)abstract
- Polyethylene glycol (PEG)-modified carbon nanotubes have been successfully employed for intra-articular delivery in mice without systemic or local toxicity. However, the fate of the delivery system itself remains to be understood. In this study 2 kDa PEG-modified single-walled carbon nanotubes (PNTs) are synthesized, and trafficking and degradation following intra-articular injection into the knee-joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs can be imaged in the knee-joint and are found to either egress from the synovial cavity or undergo biodegradation over a period of 3 weeks. Raman analysis discloses that PNTs are oxidatively degraded mainly in the chondrocyte-rich cartilage and meniscus regions while PNTs can also be detected in the synovial membrane regions, where macrophages can be found. Furthermore, using murine chondrocyte (ATDC-5) and macrophage (RAW264.7) cell lines, biodegradation of PNTs in activated, nitric oxide (NO)-producing chondrocytes, which is blocked upon pharmacological inhibition of inducible nitric oxide synthase (iNOS), can be shown. Biodegradation of PNTs in macrophages is also noted, but after a longer period of incubation. Finally, cell-free degradation of PNTs upon incubation with the peroxynitrite-generating compound, SIN-1 is demonstrated. The present study paves the way for the use of PNTs as delivery systems in the treatment of diseases of the joint.
|
|
| 4. |
- El-Sayed, Ramy, et al.
(author)
-
Single-Walled Carbon Nanotubes Inhibit the Cytochrome P450 Enzyme, CYP3A4
- 2016
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- We report a detailed computational and experimental study of the interaction of single-walled carbon nanotubes (SWCNTs) with the drug-metabolizing cytochrome P450 enzyme, CYP3A4. Dose-dependent inhibition of CYP3A4-mediated conversion of the model compound, testosterone, to its major metabolite, 6 beta-hydroxy testosterone was noted. Evidence for a direct interaction between SWCNTs and CYP3A4 was also provided. The inhibition of enzyme activity was alleviated when SWCNTs were pre-coated with bovine serum albumin. Furthermore, covalent functionalization of SWCNTs with polyethylene glycol (PEG) chains mitigated the inhibition of CYP3A4 enzymatic activity. Molecular dynamics simulations suggested that inhibition of the catalytic activity of CYP3A4 is mainly due to blocking of the exit channel for substrates/products through a complex binding mechanism. This work suggests that SWCNTs could interfere with metabolism of drugs and other xenobiotics and provides a molecular mechanism for this toxicity. Our study also suggests means to reduce this toxicity, eg., by surface modification.
|
|
| 5. |
- Fadeel, Bengt, et al.
(author)
-
Keeping it real : The importance of material characterization in nanotoxicology
- 2015
-
In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 468:3, s. 498-503
-
Research review (peer-reviewed)abstract
- Nanomaterials are small and the small size and corresponding large surface area of nanomaterials confers specific properties, making these materials desirable for various applications, not least in medicine. However, it is pertinent to ask whether size is the only property that matters for the desirable or detrimental effects of nanomaterials? Indeed, it is important to know not only what the material looks like, but also what it is made of, as well as how the material interacts with its biological surroundings. It has been suggested that guidelines should be implemented on the types of information required in terms of physicochemical characterization of nanomaterials for toxicological studies in order to improve the quality and relevance of the published results. This is certainly a key issue, but it is important to keep in mind that material characterization should be fit-for-purpose, that is, the information gathered should be relevant for the end-points being studied.
|
|
| 6. |
- Gupta, Govind, et al.
(author)
-
Development of Microfluidic, Serum-Free Bronchial Epithelial Cells-on-a-Chip to Facilitate a More Realistic In vitro Testing of Nanoplastics
- 2021
-
In: Frontiers in Toxicology. - : Frontiers Media SA. - 2673-3080. ; 3
-
Journal article (peer-reviewed)abstract
- Most cell culture models are static, but the cellular microenvironment in the body is dynamic. Here, we established a microfluidic-based in vitro model of human bronchial epithelial cells in which cells are stationary, but nutrient supply is dynamic, and we used this system to evaluate cellular uptake of nanoparticles. The cells were maintained in fetal calf serum-free and bovine pituitary extract-free cell culture medium. BEAS-2B, an immortalized, non-tumorigenic human cell line, was used as a model and the cells were grown in a chip within a microfluidic device and were briefly infused with amorphous silica (SiO2) nanoparticles or polystyrene (PS) nanoparticles of similar primary sizes but with different densities. For comparison, tests were also performed using static, multi-well cultures. Cellular uptake of the fluorescently labeled particles was investigated by flow cytometry and confocal microscopy. Exposure under dynamic culture conditions resulted in higher cellular uptake of the PS nanoparticles when compared to static conditions, while uptake of SiO2 nanoparticles was similar in both settings. The present study has shown that it is feasible to grow human lung cells under completely animal-free conditions using a microfluidic-based device, and we have also found that cellular uptake of PS nanoparticles aka nanoplastics is highly dependent on culture conditions. Hence, traditional cell cultures may not accurately reflect the uptake of low-density particles, potentially leading to an underestimation of their cellular impact.
|
|
| 7. |
- Mukherjee, Sourav P., et al.
(author)
-
Graphene oxide is degraded by neutrophils and the degradation products are non-genotoxic
- 2018
-
In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 10:3, s. 1180-1188
-
Journal article (peer-reviewed)abstract
- Neutrophils were previously shown to digest oxidized carbon nanotubes through a myeloperoxidase (MPO)-dependent mechanism, and graphene oxide (GO) was found to undergo degradation when incubated with purified MPO, but there are no studies to date showing degradation of GO by neutrophils. Here we produced endotoxin-free GO by a modified Hummers' method and asked whether primary human neutrophils stimulated to produce neutrophil extracellular traps or activated to undergo degranulation are capable of digesting GO. Biodegradation was assessed using a range of techniques including Raman spectroscopy, transmission electron microscopy, atomic force microscopy, and mass spectrometry. GO sheets of differing lateral dimensions were effectively degraded by neutrophils. As the degradation products could have toxicological implications, we also evaluated the impact of degraded GO on the bronchial epithelial cell line BEAS-2B. MPO-degraded GO was found to be non-cytotoxic and did not elicit any DNA damage. Taken together, these studies have shown that neutrophils can digest GO and that the biodegraded GO is non-toxic for human lung cells.
|
|
