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Engineering Molecular Recognition with Bio-mimetic Polymers on Single Walled Carbon Nanotubes
Published on: January 10, 2017
Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes
Anika Kaufmann1,2, Silke Hampel3, Christiane Rieger4
1Chair of Biochemistry, Department of Chemistry, Technische Universität Dresden, Bergstraße 66, 01069, Dresden, Germany.
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.
Insights
Functionalized multi-walled carbon nanotubes (MWCNT) show promise for delivering antisense oligodeoxynucleotides (AS-ODN) to bladder cancer cells. These nanotransporters facilitate drug delivery and release, offering a novel approach for bladder cancer therapy.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Materials Science
Background:
- Antisense oligodeoxynucleotides (AS-ODN) offer a novel therapeutic strategy for bladder cancer (BCa) beyond conventional chemotherapy.
- Efficient delivery of AS-ODN to bladder cancer cells is crucial for effective treatment.
- Multi-walled carbon nanotubes (MWCNT) present a potential nanocarrier system for local AS-ODN delivery to the urothelium.
Purpose of the Study:
- To synthesize and characterize pristine and functionalized MWCNT for AS-ODN delivery.
- To evaluate the physicochemical properties, biocompatibility, cellular uptake, and mucoadhesive characteristics of MWCNT.
- To assess the binding capacity and stability of AS-ODN attached to MWCNT via carrier strand oligodeoxynucleotides (CS-ODN).
Main Methods:
- Synthesis of pristine and hydrophilic moiety-functionalized MWCNT (MWCNT-OH, -COOH, -NH2, -SH).
- Assessment of MWCNT physicochemical properties, dispersibility, and stability.
- Biocompatibility assays, cellular uptake studies in BCa cells, and mucoadhesion tests on mouse bladders.
- Hybridization of CS-ODN to MWCNT via adsorption and covalent binding, followed by AS-ODN attachment and release studies.
Main Results:
- Functionalized MWCNT exhibited improved dispersibility and stability.
- MWCNT-OH, MWCNT-NH2, and MWCNT-SH demonstrated high biocompatibility.
- All MWCNT types were internalized by BCa cells, with MWCNT-OH showing the highest uptake.
- MWCNT adhered to the urothelium, and CS-ODN could be effectively attached and loaded with AS-ODN.
- Therapeutic AS-ODN demonstrated reversible release from CS-ODN-MWCNT conjugates under experimental and physiological conditions.
Conclusions:
- Functionalized MWCNT are biocompatible and capable of delivering AS-ODN to bladder cancer cells.
- MWCNT show potential as nanotransporters for localized antisense therapy in bladder cancer treatment.
- Further research into MWCNT-based drug delivery systems could advance bladder cancer therapeutics.
