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Chitosan enhances gene delivery of oligonucleotide complexes with magnetic nanoparticles–cell-penetrating peptide
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.ORCID iD: 0000-0002-6189-3020
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Assuit University, Egypt.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2018 (English)In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 33, no 3, p. 392-401Article in journal (Refereed) Published
Abstract [en]

Gene-based therapies, including the delivery of oligonucleotides, offer promising methods for the treatment of cancer cells. However, they have various limitations including low efficiency. Herein, cell-penetrating peptides (CPPs)-conjugated chitosan-modified iron oxide magnetic nanoparticles (CPPs-CTS@MNPs) with high biocompatibility as well as high efficiency were tested for the delivery of oligonucleotides such as plasmid pGL3, splice correction oligonucleotides, and small-interfering RNA. A biocompatible nanocomposite, in which CTS@MNPs was incorporated in non-covalent complex with CPPs-oligonucleotide, is developed. Modifying the surface of magnetic nanoparticles with cationic chitosan-modified iron oxide improved the performance of magnetic nanoparticles-CPPs for oligonucleotide delivery. CPPs-CTS@MNPs complexes enhance oligonucleotide transfection compared to CPPs@MNPs or CPPs. The hydrophilic character of CTS@MNPs improves complexation with plasmid pGL3, splice correction oligonucleotides, and small-interfering RNA payload, which consequently resulted in not only strengthening the colloidal stability of the constructed complex but also improving their biocompatibility. Transfection using PF14-splice correction oligonucleotides-CTS@MNPs showed sixfold increase of the transfection compared to splice correction oligonucleotides-PF14 that showed higher transfection than the commercially available lipid-based vector Lipofectamine™ 2000. Nanoscaled CPPs-CTS@MNPs comprise a new family of biomaterials that can circumvent some of the limitations of CPPs or magnetic nanoparticles.

Place, publisher, year, edition, pages
2018. Vol. 33, no 3, p. 392-401
Keywords [en]
Cell-penetrating peptides, magnetic nanoparticles, chitosan, gene delivery, small-interfering RNA, splice correction oligonucleotides
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-160327DOI: 10.1177/0885328218796623ISI: 000444975600006OAI: oai:DiVA.org:su-160327DiVA, id: diva2:1249215
Available from: 2018-09-18 Created: 2018-09-18 Last updated: 2018-10-15Bibliographically approved

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Dowaidar, MoatazAbdelhamid, Hani NasserHällbrink, MattiasLangel, ÜloZou, Xiaodong
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Department of Biochemistry and BiophysicsDepartment of Materials and Environmental Chemistry (MMK)
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