Slow release and delivery of antisense oligonucleotide drug by self-assembled peptide amphiphile nanofibers

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buir.contributor.authorBulut, Selma
buir.contributor.authorErkal, Turan S.
buir.contributor.authorToksoz, Sıla
buir.contributor.authorTekinay, Ayse B.
buir.contributor.authorTekinay, Turgay
buir.contributor.authorGüler, Mustafa O.
dc.citation.epage3014en_US
dc.citation.issueNumber8en_US
dc.citation.spage3007en_US
dc.citation.volumeNumber12en_US
dc.contributor.authorBulut, Selmaen_US
dc.contributor.authorErkal, Turan S.en_US
dc.contributor.authorToksoz, Sılaen_US
dc.contributor.authorTekinay, Ayse B.en_US
dc.contributor.authorTekinay, Turgayen_US
dc.contributor.authorGüler, Mustafa O.en_US
dc.date.accessioned2016-02-08T09:51:39Z
dc.date.available2016-02-08T09:51:39Z
dc.date.issued2011en_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.departmentAysel Sabuncu Brain Research Center (BAM)en_US
dc.description.abstractAntisense oligonucleotides provide a promising therapeutic approach for several disorders including cancer. Chemical stability, controlled release, and intracellular delivery are crucial factors determining their efficacy. Gels composed of nanofibrous peptide network have been previously suggested as carriers for controlled delivery of drugs to improve stability and to provide controlled release, but have not been used for oligonucleotide delivery. In this work, a self-assembled peptide nanofibrous system is formed by mixing a cationic peptide amphiphile (PA) with Bcl-2 antisense oligodeoxynucleotide (ODN), G3139, through electrostatic interactions. The self-assembly of PA-ODN gel was characterized by circular dichroism, rheology, atomic force microscopy (AFM) and scanning electron microscopy (SEM). AFM and SEM images revealed establishment of the nanofibrous PA-ODN network. Due to the electrostatic interactions between PA and ODN, ODN release can be controlled by changing PA and ODN concentrations in the PA-ODN gel. Cellular delivery of the ODN by PA-ODN nanofiber complex was observed by using fluorescently labeled ODN molecule. Cells incubated with PA-ODN complex had enhanced cellular uptake compared to cells incubated with naked ODN. Furthermore, Bcl-2 mRNA amounts were lower in MCF-7 human breast cancer cells in the presence of PA-ODN complex compared to naked ODN and mismatch ODN evidenced by quantitative RT-PCR studies. These results suggest that PA molecules can control ODN release, enhance cellular uptake and present a novel efficient approach for gene therapy studies and oligonucleotide based drug delivery. © 2011 American Chemical Society.en_US
dc.description.provenanceMade available in DSpace on 2016-02-08T09:51:39Z (GMT). No. of bitstreams: 1 bilkent-research-paper.pdf: 70227 bytes, checksum: 26e812c6f5156f83f0e77b261a471b5a (MD5) Previous issue date: 2011en
dc.identifier.doi10.1021/bm200641een_US
dc.identifier.issn1525-7797
dc.identifier.urihttp://hdl.handle.net/11693/21827
dc.language.isoEnglishen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/bm200641een_US
dc.source.titleBiomacromoleculesen_US
dc.titleSlow release and delivery of antisense oligonucleotide drug by self-assembled peptide amphiphile nanofibersen_US
dc.typeArticleen_US

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