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Article: Treatment of Wilms’ nephroblastoma cancer cells via EGFR targeting of dactinomycin loaded DNA-nanowires
Title | Treatment of Wilms’ nephroblastoma cancer cells via EGFR targeting of dactinomycin loaded DNA-nanowires |
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Authors | |
Keywords | Dactinomycin (DCTM) DNA-nanowires (D-NWs) Epidermal growth factor (EGF) EGFR (receptors) Resistant cancer |
Issue Date | 2021 |
Publisher | Korean Society of Pharmaceutical Sciences and Technology. The Journal's web site is located at http://www.springer.com/biomed/journal/40005 |
Citation | Journal of Pharmaceutical Investigation, 2021, v. 51, p. 233-242 How to Cite? |
Abstract | Purpose:
Dactinomycin (DCTM) is a highly cytotoxic hydrophobic drug requiring robust nanomaterials for uniformed water dispersion and safe delivery to tumor site avoiding exposure to healthy cells.
Methods:
DNA triangulation produces sturdier two-dimensional nanostructures through the polymerization of DNA-triangles by sticky ends cohesion in the form of DNA-nanosheets. The curvature of the B-form (right twisted) DNA causes the coiling of the DNA-nanosheets into DNA-nanowires (D-NWs) structures. DNA-triangles scaffolded by the short circular templates (84-NT) are stiffer in topology giving rise to compact D-NWs for DCTM loading, and cellular delivery. The PAGE gel analysis was performed to assess the polymerization of the DNA-triangles to observe restricted electrophoretic mobility, and attainment of a single sharp band. The morphology and compactness of the D-NWs were confirmed by the AFM analysis and confocal imaging. Epidermal growth factor (EGF) functionalization of the D-NWs was performed through amide chemistry using amino-modified DNA strands reacting with the carboxylic group of EGF for EGFR targeting. EGFR is highly expressed on NB-OK-1 Wilms’ tumor nephroblastoma cancer cells. DCTM loading onto D-NWs was carried out through intercalation between the base pairs of GC rich DNA duplex by physical mixing/incubation, and was confirmed through the UV peak shift analysis and confocal imaging. Cell internalizations and the cytotoxic effects were monitored via confocal imaging, MTT assay, and flow cytometry.
Results:
AFM images of the synthesized D-NWs showed that polymerization of DNA-triangles was successful with the length ranging from 4 to 6 µm, and width ranging from 80 to 120 nm. EGF functionalization was confirmed through the confocal microscopy after labeling EGF with the FITC hook conjugating dye. The slight UV shift (> 15 nm) confirmed DCTM loading onto D-NWs. Blank D-NWs showed biocompatibility to the cells at different (low to high) concentrations (10 µM to 640 µM). MTT assay revealed that DCTM loaded D-NWs showed a dose-dependent (0.25–128 nM) decrease in cell viability.
Conclusion:
EGF functionalized D-NWs effectively targeted the EGFR rich NB-OK-1 cancer cells compared to the control HEK293/D75 cells lacking EGFR (receptors). By these results, we can expect similar site-specific targeted treatment if administered systemically. |
Persistent Identifier | http://hdl.handle.net/10722/295247 |
ISSN | 2023 Impact Factor: 5.3 2023 SCImago Journal Rankings: 0.816 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Baig, MMFA | - |
dc.contributor.author | Zhang, C | - |
dc.contributor.author | Akhtar, MF | - |
dc.contributor.author | Saleem, A | - |
dc.contributor.author | Naveed, N | - |
dc.date.accessioned | 2021-01-11T13:57:25Z | - |
dc.date.available | 2021-01-11T13:57:25Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Journal of Pharmaceutical Investigation, 2021, v. 51, p. 233-242 | - |
dc.identifier.issn | 2093-5552 | - |
dc.identifier.uri | http://hdl.handle.net/10722/295247 | - |
dc.description.abstract | Purpose: Dactinomycin (DCTM) is a highly cytotoxic hydrophobic drug requiring robust nanomaterials for uniformed water dispersion and safe delivery to tumor site avoiding exposure to healthy cells. Methods: DNA triangulation produces sturdier two-dimensional nanostructures through the polymerization of DNA-triangles by sticky ends cohesion in the form of DNA-nanosheets. The curvature of the B-form (right twisted) DNA causes the coiling of the DNA-nanosheets into DNA-nanowires (D-NWs) structures. DNA-triangles scaffolded by the short circular templates (84-NT) are stiffer in topology giving rise to compact D-NWs for DCTM loading, and cellular delivery. The PAGE gel analysis was performed to assess the polymerization of the DNA-triangles to observe restricted electrophoretic mobility, and attainment of a single sharp band. The morphology and compactness of the D-NWs were confirmed by the AFM analysis and confocal imaging. Epidermal growth factor (EGF) functionalization of the D-NWs was performed through amide chemistry using amino-modified DNA strands reacting with the carboxylic group of EGF for EGFR targeting. EGFR is highly expressed on NB-OK-1 Wilms’ tumor nephroblastoma cancer cells. DCTM loading onto D-NWs was carried out through intercalation between the base pairs of GC rich DNA duplex by physical mixing/incubation, and was confirmed through the UV peak shift analysis and confocal imaging. Cell internalizations and the cytotoxic effects were monitored via confocal imaging, MTT assay, and flow cytometry. Results: AFM images of the synthesized D-NWs showed that polymerization of DNA-triangles was successful with the length ranging from 4 to 6 µm, and width ranging from 80 to 120 nm. EGF functionalization was confirmed through the confocal microscopy after labeling EGF with the FITC hook conjugating dye. The slight UV shift (> 15 nm) confirmed DCTM loading onto D-NWs. Blank D-NWs showed biocompatibility to the cells at different (low to high) concentrations (10 µM to 640 µM). MTT assay revealed that DCTM loaded D-NWs showed a dose-dependent (0.25–128 nM) decrease in cell viability. Conclusion: EGF functionalized D-NWs effectively targeted the EGFR rich NB-OK-1 cancer cells compared to the control HEK293/D75 cells lacking EGFR (receptors). By these results, we can expect similar site-specific targeted treatment if administered systemically. | - |
dc.language | eng | - |
dc.publisher | Korean Society of Pharmaceutical Sciences and Technology. The Journal's web site is located at http://www.springer.com/biomed/journal/40005 | - |
dc.relation.ispartof | Journal of Pharmaceutical Investigation | - |
dc.rights | Accepted Manuscript (AAM) This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: https://doi.org/[insert DOI] | - |
dc.subject | Dactinomycin (DCTM) | - |
dc.subject | DNA-nanowires (D-NWs) | - |
dc.subject | Epidermal growth factor (EGF) | - |
dc.subject | EGFR (receptors) | - |
dc.subject | Resistant cancer | - |
dc.title | Treatment of Wilms’ nephroblastoma cancer cells via EGFR targeting of dactinomycin loaded DNA-nanowires | - |
dc.type | Article | - |
dc.identifier.email | Baig, MMFA: faran@HKUCC-COM.hku.hk | - |
dc.identifier.email | Zhang, C: zhangcf@hku.hk | - |
dc.identifier.authority | Baig, MMFA=rp02755 | - |
dc.identifier.authority | Zhang, C=rp01408 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1007/s40005-020-00509-5 | - |
dc.identifier.scopus | eid_2-s2.0-85098512946 | - |
dc.identifier.hkuros | 320890 | - |
dc.identifier.volume | 51 | - |
dc.identifier.spage | 233 | - |
dc.identifier.epage | 242 | - |
dc.identifier.isi | WOS:000604064100001 | - |
dc.publisher.place | Republic of Korea | - |