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Article: Targeting folate receptors (α1) to internalize the bleomycin loaded DNA-nanotubes into prostate cancer xenograft CWR22R cells

TitleTargeting folate receptors (α1) to internalize the bleomycin loaded DNA-nanotubes into prostate cancer xenograft CWR22R cells
Authors
KeywordsBleomycin (BM)
CWR22R (resistant prostate cancer xenograft) cells
Folate receptor/alpha (FRα)
FRα-targeting antibodies
DNA-nanotubes (D-NT)
Issue Date2020
Citation
Journal of Molecular Liquids, 2020, v. 316, article no. 113785 How to Cite?
Abstract© 2020 Elsevier B.V. DNA-nanotechnology based on DNA scaffolding technique is an established approach to formulate water-miscible nano-structural frameworks. We have designed the hydrophilic DNA-nanotubes (D-NTs) as a (water-soluble) vehicle to encapsulate a water-insoluble DNA-intercalating anticancer drug. Bleomycin (BM) is a model hydrophobic anticancer drug used in this study capable to bind with the D-NTs to formulate BM loaded D-NTs. This BM@D-NTs system was evaluated for the improvement of the in vitro anti-cancer effects on the resistant prostate cancer xenograft CWR22R cells, over-expressed with the folate receptors/alpha (FRα). D-NTs were functionalized with the FRα-targeting antibodies to interact with the FRα (receptors) highly expressed on the resistant prostate cancer xenograft CWR22R cells. D-NTs not only increased the aqueous miscibility/dispersibility of BM but also enhanced the therapeutic efficiency as a targeted (site-specific) drug delivery system. D-NTs synthesis was achieved by sticky ends cohesions of DNA triangular tiles. DNA triangles were self-assembled from a freshly circularized short scaffold chain (84-NT) by annealing with the various staple strands. The polymerization of the triangular tiles gave rise to DNA-nanosheet lattices which underwent morphological transition guided by the twists in the DNA duplexes. This DNA double helix curvature caused self-coiling of the DNA 2D nano-sheets to condense into D-NTs morphology. Native-Page gel experiment showed decreased electrophoretic mobility down the gel confirming the successful execution of the polymerized lattices via sticky ends cohesion of the DNA-triangles. The final morphology and self-coiling of 2D DNA nano-sheets were confirmed through atomic force microscopy (AFM) showed the successful synthesis of D-NTs having diameter 3 to 5 μm and length 200 to 600 nm. BM was loaded onto D-NTs via incubation of hydro-alcoholic solution of the BM with the aqueous solution of D-NTs followed by the evaporation of alcohol and intercalation of the BM onto D-NTs. The intercalation of BM onto D-NTs was confirmed by UV-shift analysis. The targeted cytotoxicity of the BM@D-NTs for the CWR22R (resistant prostate cancer xenograft) cells was confirmed through MTT assay and the flow cytometry compared to the highly compatible empty D-NTs. Confocal microscopy revealed the time-dependent transfection of BM@D-NTs into CWR22R cells compared to the control cell line.
Persistent Identifierhttp://hdl.handle.net/10722/293136
ISSN
2023 Impact Factor: 5.3
2023 SCImago Journal Rankings: 0.918
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBaig, Mirza Muhammad Faran Ashraf-
dc.contributor.authorLai, Wing Fu-
dc.contributor.authorAkhtar, Muhammad Furqan-
dc.contributor.authorSaleem, Ammara-
dc.contributor.authorMikrani, Reyaj-
dc.contributor.authorFarooq, Muhammad Asim-
dc.contributor.authorAhmed, Saud Asif-
dc.contributor.authorTahir, Anum-
dc.contributor.authorNaveed, Muhammad-
dc.contributor.authorAbbas, Muhammad-
dc.contributor.authorAnsari, Muhammad Tayyab-
dc.date.accessioned2020-11-19T09:02:04Z-
dc.date.available2020-11-19T09:02:04Z-
dc.date.issued2020-
dc.identifier.citationJournal of Molecular Liquids, 2020, v. 316, article no. 113785-
dc.identifier.issn0167-7322-
dc.identifier.urihttp://hdl.handle.net/10722/293136-
dc.description.abstract© 2020 Elsevier B.V. DNA-nanotechnology based on DNA scaffolding technique is an established approach to formulate water-miscible nano-structural frameworks. We have designed the hydrophilic DNA-nanotubes (D-NTs) as a (water-soluble) vehicle to encapsulate a water-insoluble DNA-intercalating anticancer drug. Bleomycin (BM) is a model hydrophobic anticancer drug used in this study capable to bind with the D-NTs to formulate BM loaded D-NTs. This BM@D-NTs system was evaluated for the improvement of the in vitro anti-cancer effects on the resistant prostate cancer xenograft CWR22R cells, over-expressed with the folate receptors/alpha (FRα). D-NTs were functionalized with the FRα-targeting antibodies to interact with the FRα (receptors) highly expressed on the resistant prostate cancer xenograft CWR22R cells. D-NTs not only increased the aqueous miscibility/dispersibility of BM but also enhanced the therapeutic efficiency as a targeted (site-specific) drug delivery system. D-NTs synthesis was achieved by sticky ends cohesions of DNA triangular tiles. DNA triangles were self-assembled from a freshly circularized short scaffold chain (84-NT) by annealing with the various staple strands. The polymerization of the triangular tiles gave rise to DNA-nanosheet lattices which underwent morphological transition guided by the twists in the DNA duplexes. This DNA double helix curvature caused self-coiling of the DNA 2D nano-sheets to condense into D-NTs morphology. Native-Page gel experiment showed decreased electrophoretic mobility down the gel confirming the successful execution of the polymerized lattices via sticky ends cohesion of the DNA-triangles. The final morphology and self-coiling of 2D DNA nano-sheets were confirmed through atomic force microscopy (AFM) showed the successful synthesis of D-NTs having diameter 3 to 5 μm and length 200 to 600 nm. BM was loaded onto D-NTs via incubation of hydro-alcoholic solution of the BM with the aqueous solution of D-NTs followed by the evaporation of alcohol and intercalation of the BM onto D-NTs. The intercalation of BM onto D-NTs was confirmed by UV-shift analysis. The targeted cytotoxicity of the BM@D-NTs for the CWR22R (resistant prostate cancer xenograft) cells was confirmed through MTT assay and the flow cytometry compared to the highly compatible empty D-NTs. Confocal microscopy revealed the time-dependent transfection of BM@D-NTs into CWR22R cells compared to the control cell line.-
dc.languageeng-
dc.relation.ispartofJournal of Molecular Liquids-
dc.subjectBleomycin (BM)-
dc.subjectCWR22R (resistant prostate cancer xenograft) cells-
dc.subjectFolate receptor/alpha (FRα)-
dc.subjectFRα-targeting antibodies-
dc.subjectDNA-nanotubes (D-NT)-
dc.titleTargeting folate receptors (α1) to internalize the bleomycin loaded DNA-nanotubes into prostate cancer xenograft CWR22R cells-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.molliq.2020.113785-
dc.identifier.scopuseid_2-s2.0-85088378136-
dc.identifier.hkuros320905-
dc.identifier.volume316-
dc.identifier.spagearticle no. 113785-
dc.identifier.epagearticle no. 113785-
dc.identifier.isiWOS:000568693000004-
dc.identifier.issnl0167-7322-

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