Cellular internalization of therapeutic oligonucleotides by peptide amphiphile nanofibers and nanospheres

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buir.contributor.authorGüler, Mustafa O.
dc.citation.epage11287en_US
dc.citation.issueNumber18en_US
dc.citation.spage11280en_US
dc.citation.volumeNumber8en_US
dc.contributor.authorMumcuoglu, D.en_US
dc.contributor.authorS. Ekiz, M.en_US
dc.contributor.authorGunay, G.en_US
dc.contributor.authorTekinay, T.en_US
dc.contributor.authorTekinay, A. B.en_US
dc.contributor.authorGüler, Mustafa O.en_US
dc.date.accessioned2018-04-12T10:51:11Z
dc.date.available2018-04-12T10:51:11Z
dc.date.issued2016-04en_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.departmentNanotechnology Research Center (NANOTAM)en_US
dc.description.abstractOligonucleotides are promising drug candidates due to the exceptionally high specificity they exhibit toward their target DNA and RNA sequences. However, their poor pharmacokinetic and pharmacodynamic properties, in conjunction with problems associated with their internalization by cells, necessitates their delivery through specialized carrier systems for efficient therapy. Here, we investigate the effects of carrier morphology on the cellular internalization mechanisms of oligonucleotides by using self-assembled fibrous or spherical peptide nanostructures. Size and geometry were both found to be important parameters for the oligonucleotide internalization process; direct penetration was determined to be the major mechanism for the internalization of nanosphere carriers, whereas nanofibers were internalized by clathrin- and dynamin-dependent endocytosis pathways. We further showed that glucose conjugation to carrier nanosystems improved cellular internalization in cancer cells due to the enhanced glucose metabolism associated with oncogenesis, and the internalization of the glucose-conjugated peptide/oligonucleotide complexes was found to be dependent on glucose transporters present on the surface of the cell membrane.en_US
dc.identifier.doi10.1021/acsami.6b01526en_US
dc.identifier.issn1944-8244
dc.identifier.urihttp://hdl.handle.net/11693/36730
dc.language.isoEnglishen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.isversionofhttps://doi.org/10.1021/acsami.6b01526en_US
dc.source.titleACS Applied Materials and Interfacesen_US
dc.subjectGlucose transportersen_US
dc.subjectGlycoconjugatesen_US
dc.subjectInternalizationen_US
dc.subjectOligonucleotide deliveryen_US
dc.subjectPeptide amphiphilesen_US
dc.subjectSelf-assemblyen_US
dc.subjectCytologyen_US
dc.subjectDNA sequencesen_US
dc.subjectGlucoseen_US
dc.subjectMolecular biologyen_US
dc.subjectNanofibersen_US
dc.subjectNanospheresen_US
dc.subjectNanosystemsen_US
dc.subjectNucleic acidsen_US
dc.subjectOligonucleotidesen_US
dc.subjectPeptidesen_US
dc.subjectPolypeptidesen_US
dc.subjectSelf assemblyen_US
dc.subjectCellular internalizationen_US
dc.subjectEndocytosis pathwayen_US
dc.subjectGlucose metabolismen_US
dc.subjectGlucose transportersen_US
dc.subjectGlucose-conjugationen_US
dc.subjectGlycoconjugatesen_US
dc.subjectInternalizationen_US
dc.subjectPeptide amphiphilesen_US
dc.subjectAmphiphilesen_US
dc.subjectClathrinen_US
dc.subjectNanofiberen_US
dc.subjectNanosphereen_US
dc.subjectOligonucleotideen_US
dc.subjectPeptideen_US
dc.subjectEndocytosisen_US
dc.subjectHumanen_US
dc.subjectClathrinen_US
dc.subjectEndocytosisen_US
dc.subjectHumansen_US
dc.subjectNanofibersen_US
dc.subjectNanospheresen_US
dc.subjectOligonucleotidesen_US
dc.subjectPeptidesen_US
dc.titleCellular internalization of therapeutic oligonucleotides by peptide amphiphile nanofibers and nanospheresen_US
dc.typeArticleen_US
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Institute of Materials Science and Nanotechnology (UNAM)
Nanotechnology Research Center (NANOTAM)