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Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells

Cancer gene therapy requires the design of non-viral vectors that carry genetic material and selectively deliver it with minimal toxicity. Non-viral vectors based on cationic natural polymers can form electrostatic complexes with negatively-charged polynucleotides such as microRNAs (miRNAs). Here we investigated the physicochemical/biophysical properties of chitosan–hsa-miRNA-145 (CS–miRNA) nanocomplexes and the biological responses of MCF-7 breast cancer cells cultured in vitro. Self-assembled CS–miRNA nanocomplexes were produced with a range of (+/−) charge ratios (from 0.6 to 8) using chitosans with various degrees of acetylation and molecular weight. The Z-average particle diameter of the complexes was <200 nm. The surface charge increased with increasing amount of chitosan. We observed that chitosan induces the base-stacking of miRNA in a concentration dependent manner. Surface plasmon resonance spectroscopy shows that complexes formed by low degree of acetylation chitosans are highly stable, regardless of the molecular weight. We found no evidence that these complexes were cytotoxic towards MCF-7 cells. Furthermore, CS–miRNA nanocomplexes with degree of acetylation 12% and 29% were biologically active, showing successful downregulation of target mRNA expression in MCF-7 cells. Our data, therefore, shows that CS–miRNA complexes offer a promising non-viral platform for breast cancer gene therapy.

Titel: Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells
Verfasser: Santos-Carballa, B.
Aaldering, Lukas
Ritzefeld, M.
Pereira, Suzana Maria Soares Santos
Sewald, N.
Moerschbacher, Bruno M.
Götte, Martin GND
Goycoolea, Francisco Martin
Organisation: FB 13: Biologie
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 01.09.2015
Publikation in MIAMI: 08.10.2015
Datum der letzten Änderung: 08.10.2015
Quelle: Scientific Reports 5 (2015) 13567, 1-15
Fachgebiete: Biowissenschaften; Biologie
Lizenz: CC BY 4.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-78219455692
Permalink: https://nbn-resolving.org/urn:nbn:de:hbz:6-78219455692
DOI: 10.1038/srep13567
ISSN: 2045-2322
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