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Article: The integrin facilitated internalization of fibronectin-functionalized camptothecin-loaded DNA-nanofibers for high-efficiency anticancer effects

TitleThe integrin facilitated internalization of fibronectin-functionalized camptothecin-loaded DNA-nanofibers for high-efficiency anticancer effects
Authors
KeywordsFibronectin (FN)
Integrin receptors
DNA-nanofibers (DNA-NFs)
Camptothecin (CMPT)
A549 cells
Issue Date2020
Citation
Drug Delivery and Translational Research, 2020, v. 10, n. 5, p. 1381-1392 How to Cite?
Abstract© 2020, Controlled Release Society. Camptothecin (CMPT) in a free form is extremely cytotoxic as well as hydrophobic drug, and is considered to be highly contagious for systemic administration. The fibronectin (FN)-functionalized DNA-based nanocarrier has been designed to load CMPT and target integrin (αvβ3) receptors which are highly expressed on the A549 cancer cells. Here, we report DNA nanocarrier in the form of DNA-nanofibers (DNA-NFs) capable of loading CMPT via strand intercalation in the GC (base pairs)-rich regions of the DNA duplex. Hence, our keen purpose was to explore the potential of DNA-NFs to load CMPT and assess the improvements of the outcomes in terms of enhanced therapeutic effects to integrin-rich A549 cancer cells with reduced cytotoxic effects to integrin-lacking HEK293 cells. DNA-NFs were formulated as a polymer of DNA triangles. DNA triangles arranged in a programmed way through the complementary overhangs present at the vertices. DNA triangles were primarily obtained through the annealing of the freshly circularized scaffold strands with the three distinct staple strands of specific sequences. The polymerized triangular tiles instead of forming two-dimensional nanosheets underwent self-coiling to give rise to DNA-NF-shaped structures. Flow cytometry and MTT assays were performed to observe cytotoxic and apoptotic effects on integrin-rich A549 cancer cells compared with the integrin-deficient HEK293 cells. AFM, native-page, and confocal experiments confirmed the polymerization of DNA triangles and the morphology of the resulting nanostructures. AFM and confocal images revealed the length of DNA-NFs to be 3–6 μm and the width from 70 to 110 nm. CMPT loading (via strands intercalation) in GC-rich regions of DNA-NFs and the FN functionalization (TAMRA tagged; red fluorescence) via amide chemistry using amino-modified strands of DNA-NFs were confirmed through the UV-shift analysis (> 10 nm shift) and confocal imaging. Blank DNA-NFs were found to be highly biocompatible in 2–640 μM concentrations. MTT assay and flow cytometry experiments revealed that CMPT-loaded DNA-NFs showed a dose-dependent decrease in the cell viability to integrin-rich A549 cancer cells compared with the integrin-deficient HEK293 cells. Conclusively, FN-functionalized, CMPT-loaded DNA-NFs effectively destroyed integrin-rich A549 cancer cells in a targeted manner compared with integrin-deficient HEK293 cells.[Figure not available: see fulltext.]
Persistent Identifierhttp://hdl.handle.net/10722/293135
ISSN
2023 Impact Factor: 5.7
2023 SCImago Journal Rankings: 0.994
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBaig, Mirza Muhammad Faran Ashraf-
dc.contributor.authorLai, Wing Fu-
dc.contributor.authorAshraf, Saba-
dc.contributor.authorSaleem, Ammara-
dc.contributor.authorAkhtar, Muhammad Furqan-
dc.contributor.authorMikrani, Reyaj-
dc.contributor.authorNaveed, Muhammad-
dc.contributor.authorSiddique, Farhan-
dc.contributor.authorTaleb, Abdoh-
dc.contributor.authorMudassir, Jahanzeb-
dc.contributor.authorKhan, Ghulam Jilany-
dc.contributor.authorAnsari, Muhammad Tayyab-
dc.date.accessioned2020-11-19T09:02:03Z-
dc.date.available2020-11-19T09:02:03Z-
dc.date.issued2020-
dc.identifier.citationDrug Delivery and Translational Research, 2020, v. 10, n. 5, p. 1381-1392-
dc.identifier.issn2190-393X-
dc.identifier.urihttp://hdl.handle.net/10722/293135-
dc.description.abstract© 2020, Controlled Release Society. Camptothecin (CMPT) in a free form is extremely cytotoxic as well as hydrophobic drug, and is considered to be highly contagious for systemic administration. The fibronectin (FN)-functionalized DNA-based nanocarrier has been designed to load CMPT and target integrin (αvβ3) receptors which are highly expressed on the A549 cancer cells. Here, we report DNA nanocarrier in the form of DNA-nanofibers (DNA-NFs) capable of loading CMPT via strand intercalation in the GC (base pairs)-rich regions of the DNA duplex. Hence, our keen purpose was to explore the potential of DNA-NFs to load CMPT and assess the improvements of the outcomes in terms of enhanced therapeutic effects to integrin-rich A549 cancer cells with reduced cytotoxic effects to integrin-lacking HEK293 cells. DNA-NFs were formulated as a polymer of DNA triangles. DNA triangles arranged in a programmed way through the complementary overhangs present at the vertices. DNA triangles were primarily obtained through the annealing of the freshly circularized scaffold strands with the three distinct staple strands of specific sequences. The polymerized triangular tiles instead of forming two-dimensional nanosheets underwent self-coiling to give rise to DNA-NF-shaped structures. Flow cytometry and MTT assays were performed to observe cytotoxic and apoptotic effects on integrin-rich A549 cancer cells compared with the integrin-deficient HEK293 cells. AFM, native-page, and confocal experiments confirmed the polymerization of DNA triangles and the morphology of the resulting nanostructures. AFM and confocal images revealed the length of DNA-NFs to be 3–6 μm and the width from 70 to 110 nm. CMPT loading (via strands intercalation) in GC-rich regions of DNA-NFs and the FN functionalization (TAMRA tagged; red fluorescence) via amide chemistry using amino-modified strands of DNA-NFs were confirmed through the UV-shift analysis (> 10 nm shift) and confocal imaging. Blank DNA-NFs were found to be highly biocompatible in 2–640 μM concentrations. MTT assay and flow cytometry experiments revealed that CMPT-loaded DNA-NFs showed a dose-dependent decrease in the cell viability to integrin-rich A549 cancer cells compared with the integrin-deficient HEK293 cells. Conclusively, FN-functionalized, CMPT-loaded DNA-NFs effectively destroyed integrin-rich A549 cancer cells in a targeted manner compared with integrin-deficient HEK293 cells.[Figure not available: see fulltext.]-
dc.languageeng-
dc.relation.ispartofDrug Delivery and Translational Research-
dc.subjectFibronectin (FN)-
dc.subjectIntegrin receptors-
dc.subjectDNA-nanofibers (DNA-NFs)-
dc.subjectCamptothecin (CMPT)-
dc.subjectA549 cells-
dc.titleThe integrin facilitated internalization of fibronectin-functionalized camptothecin-loaded DNA-nanofibers for high-efficiency anticancer effects-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s13346-020-00820-6-
dc.identifier.pmid32661832-
dc.identifier.scopuseid_2-s2.0-85087924830-
dc.identifier.hkuros320906-
dc.identifier.volume10-
dc.identifier.issue5-
dc.identifier.spage1381-
dc.identifier.epage1392-
dc.identifier.eissn2190-3948-
dc.identifier.isiWOS:000548095000001-
dc.identifier.issnl2190-393X-

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