Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-017-0288-z |
| _version_ | 1811302321504649216 |
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| author | Anika Kaufmann Silke Hampel Christiane Rieger David Kunhardt Darja Schendel Susanne Füssel Bernd Schwenzer Kati Erdmann |
| author_facet | Anika Kaufmann Silke Hampel Christiane Rieger David Kunhardt Darja Schendel Susanne Füssel Bernd Schwenzer Kati Erdmann |
| author_sort | Anika Kaufmann |
| collection | DOAJ |
| description | Abstract 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. |
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| format | Article |
| id | doaj.art-abd1a16f90734ac8967c3632a5b55d23 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-13T07:25:54Z |
| publishDate | 2017-07-01 |
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| series | Journal of Nanobiotechnology |
| spelling | doaj.art-abd1a16f90734ac8967c3632a5b55d232022-12-22T02:56:28ZengBMCJournal of Nanobiotechnology1477-31552017-07-0115111510.1186/s12951-017-0288-zSystematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubesAnika Kaufmann0Silke Hampel1Christiane Rieger2David Kunhardt3Darja Schendel4Susanne Füssel5Bernd Schwenzer6Kati Erdmann7Chair of Biochemistry, Department of Chemistry, Technische Universität DresdenLeibniz Institute for Solid State and Materials Research DresdenDepartment of Urology, University Hospital Carl Gustav Carus, Technische Universität DresdenLeibniz Institute for Solid State and Materials Research DresdenDepartment of Urology, University Hospital Carl Gustav Carus, Technische Universität DresdenDepartment of Urology, University Hospital Carl Gustav Carus, Technische Universität DresdenChair of Biochemistry, Department of Chemistry, Technische Universität DresdenDepartment of Urology, University Hospital Carl Gustav Carus, Technische Universität DresdenAbstract 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.http://link.springer.com/article/10.1186/s12951-017-0288-zAntisense oligodeoxynucleotidesBiocompatibilityBladder cancerCarbon nanotubesCarrier strandFunctionalization |
| spellingShingle | Anika Kaufmann Silke Hampel Christiane Rieger David Kunhardt Darja Schendel Susanne Füssel Bernd Schwenzer Kati Erdmann Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes Journal of Nanobiotechnology Antisense oligodeoxynucleotides Biocompatibility Bladder cancer Carbon nanotubes Carrier strand Functionalization |
| title | Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes |
| title_full | Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes |
| title_fullStr | Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes |
| title_full_unstemmed | Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes |
| title_short | Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes |
| title_sort | systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi walled carbon nanotubes |
| topic | Antisense oligodeoxynucleotides Biocompatibility Bladder cancer Carbon nanotubes Carrier strand Functionalization |
| url | http://link.springer.com/article/10.1186/s12951-017-0288-z |
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