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DDC: 610 × Subject: Carbon nanotubes ×

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    Surface defects reduce Carbon Nanotube toxicity in vitro
    (Amsterdam [u.a.] : Elsevier Science, 2019) Requardt, Hendrik; Braun, Armin; Steinberg, Pablo; Hampel, Silke; Hansen, Tanja
    The cytotoxicity of two different types of Multi-walled Carbon Nanotubes (MWCNTs)in A549 lung epithelial cells and HepG2 hepatocytes was investigated. One MWCNT still contained iron that was used as a catalyst during production, while the other one had all iron removed in a post-production heat treatment resulting in significantly fewer surface defects. The WST-8 assay was applied to test cell viability. To check the integrity of the cell membrane, we performed the lactate dehydrogenases assay (LDH)and measured the cellular production of reactive oxygen species (ROS). Finally, to examine cell proliferation, we conducted a cell cycle analysis. The results showed a dose- and time-dependent decrease in cell viability for both MWCNTs in both cell types. Moreover, a dose- and time-dependent increase in LDH leakage was detected, thereby indicating a decreased membrane integrity. The production of ROS was significantly increased in the case of the heat-treated MWCNTs. The heat-treated MWCNTs showed significantly stronger adverse effects when compared to the non-treated MWCNTs. Additionally, the heat-treated MWCNTs induced a dose-dependent cell cycle arrest in A549 cells. Both MWCNTs induced a significant cytotoxicity, whereby the heat treatment, leading to a decrease in surface defects, further increased the indicated adverse effects. © 2019 The Authors
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    Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes
    (London : Biomed Central, 2017) Kaufmann, Anika; Hampel, Silke; Rieger, Christiane; Kunhardt, David; Schendel, Darja; Füssel, Susanne; Schwenzer, Bernd; Erdmann, Kati
    Background: In addition to conventional chemotherapeutics, nucleic acid-based therapeutics like antisense oligodeoxynucleotides (AS-ODN) represent a novel approach for the treatment of bladder cancer (BCa). An efficient delivery of AS-ODN to the urothelium and then into cancer cells might be achieved by the local application of multi-walled carbon nanotubes (MWCNT). In the present study, pristine MWCNT and MWCNT functionalized with hydrophilic moieties were synthesized and then investigated regarding their physicochemical characteristics, dispersibility, biocompatibility, cellular uptake and mucoadhesive properties. Finally, their binding capacity for AS-ODN via hybridization to carrier strand oligodeoxynucleotides (CS-ODN), which were either non-covalently adsorbed or covalently bound to the different MWCNT types, was evaluated. Results: Pristine MWCNT were successfully functionalized with hydrophilic moieties (MWCNT-OH, -COOH, -NH2, -SH), which led to an improved dispersibility and an enhanced dispersion stability. A viability assay revealed that MWCNT-OH, MWCNT-NH2 and MWCNT-SH were most biocompatible. All MWCNT were internalized by BCa cells, whereupon the highest uptake was observed for MWCNT-OH with 40% of the cells showing an engulfment. Furthermore, all types of MWCNT could adhere to the urothelium of explanted mouse bladders, but the amount of the covered urothelial area was with 2-7% rather low. As indicated by fluorescence measurements, it was possible to attach CS-ODN by adsorption and covalent binding to functionalized MWCNT. Adsorption of CS-ODN to pristine MWCNT, MWCNT-COOH and MWCNT-NH2 as well as covalent coupling to MWCNT-NH2 and MWCNT-SH resulted in the best binding capacity and stability. Subsequently, therapeutic AS-ODN could be hybridized to and reversibly released from the CS-ODN coupled via both strategies to the functionalized MWCNT. The release of AS-ODN at experimental conditions (80 °C, buffer) was most effective from CS-ODN adsorbed to MWCNT-OH and MWCNT-NH2 as well as from CS-ODN covalently attached to MWCNT-COOH, MWCNT-NH2 and MWCNT-SH. Furthermore, we could exemplarily demonstrate that AS-ODN could be released following hybridization to CS-ODN adsorbed to MWCNT-OH at physiological settings (37 °C, urine). Conclusions: In conclusion, functionalized MWCNT might be used as nanotransporters in antisense therapy for the local treatment of BCa.