Oligonucleotide delivery with cell surface binding and cell penetrating peptide amphiphile nanospheres

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buir.contributor.authorMumcuoğlu, Didem
buir.contributor.authorSardan, Melis
buir.contributor.authorGüler, Mustafa O.
buir.contributor.authorTekinay, Ayşe. B.
dc.citation.epage1591en_US
dc.citation.issueNumber5en_US
dc.citation.spage1584en_US
dc.citation.volumeNumber12en_US
dc.contributor.authorMumcuoğlu, Didemen_US
dc.contributor.authorSardan, Melisen_US
dc.contributor.authorTekinay, T.en_US
dc.contributor.authorGüler, Mustafa O.en_US
dc.contributor.authorTekinay, Ayşe. B.en_US
dc.date.accessioned2015-07-28T12:03:19Z
dc.date.available2015-07-28T12:03:19Z
dc.date.issued2015en_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.departmentNanotechnology Research Center (NANOTAM)en_US
dc.departmentAysel Sabuncu Brain Research Center (BAM)en_US
dc.description.abstractA drug delivery system designed specifically for oligonucleotide therapeutics can ameliorate the problems associated with the in vivo delivery of these molecules. The internalization of free oligonudeotides is challenging, and cytotoxicity is the main obstacle for current transfection vehicles. To develop nontoxic delivery vehicles for efficient transfection of oligonudeotides, we designed a self-assembling peptide amphiphile (PA) nanosphere delivery system decorated with cell penetrating peptides (CPPs) containing multiple arginine residues (R-4 and R-8), and a cell surface binding peptide (KRSR), and report the efficiency of this system in delivering G-3129, a Bcl-2 antisense oligonucleotide (AON). PA/AON (peptide amphiphile/antisense oligonucleotide) complexes were characterized with regards to their size and secondary structure, and their cellular internalization efficiencies were evaluated. The effect of the number of arginine residues on the cellular internalization was investigated by both flow cytometry and confocal imaging, and the results revealed that uptake efficiency improved as the number of arginines in the sequence increased. The combined effect of cell penetration and surface binding property on the cellular internalization and its uptake mechanism was also evaluated by mixing R-8-PA and KRSR-PA. R-8 and R-8/KRSR decorated PAs were found to drastically increase the internalization of AONs compared to nonbioactive PA control. Overall, the KRSR-decorated self-assembled PA nanospheres were demonstrated to be noncytotoxic delivery vectors with high transfection rates and may serve as a promising delivery system for AONs.en_US
dc.description.provenanceMade available in DSpace on 2015-07-28T12:03:19Z (GMT). No. of bitstreams: 1 11527.pdf: 6560573 bytes, checksum: b2f3b1d9090dab97e140b11c215f974e (MD5)en_US
dc.identifier.doi10.1021/acs.molpharmaceut.5b00007en_US
dc.identifier.issn1584−1591
dc.identifier.urihttp://hdl.handle.net/11693/12834
dc.language.isoEnglishen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/acs.molpharmaceut.5b00007en_US
dc.source.titleMolecular Pharmeceuticsen_US
dc.titleOligonucleotide delivery with cell surface binding and cell penetrating peptide amphiphile nanospheresen_US
dc.typeArticleen_US

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