Journal
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 15, Issue 1, Pages 69-82Publisher
SHENYANG PHARMACEUTICAL UNIV
DOI: 10.1016/j.ajps.2018.10.006
Keywords
MicroRNA; PEI nanogels; Anti-miR-21; Gene delivery; Cisplatin resistance
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Funding
- Shiraz University of Medical Sciences [SUMS-93-01-05-8630]
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A series of branched polyethylenimine (PEI) modifications including PEGylation (PEG2k-PEI) for steric shielding, redox-sensitive crosslinking for synthesis PEG2k-PEI-ss nanogels and subsequent carboxymethylation (PEG2k-CMPEI-ss) for modulation of the polymer pka have been introduced for cellular delivery of Anti-miR-21. The synthesis was characterized using H-1 NMR, FTIR, TNBS, potentiometric titration, particle size and potential. Loading of Anti-miR-21 at various N/P ratios was investigated by gel retardation, ethidium bromide dye exclusion, heparin sulfate competition and DNase I digestion experiments. The miR-21 silencing was measured by stem-loop RT PCR in A2780 ovarian cancer cell lines whether it is sensitive to resistant to cisplatin. It has been shown that PEG2k-CMPEI-ss was well suited for delivery of Anti-miR-21 in terms of nucleic acid loading, preservation against extracellular matrix and nucleases and sequence-specific silencing of miRNA-21 in vitro. Moreover, it has been demonstrated that pre-treating cells with Anti-miR-21 loaded nanogels can sensitize them to cis-Pt even at non-toxic concentraions. The results indicate that PEG2k-CMPEIss mediated microRNA delivery can be considered as a novel strategy for ovarian cancer therapy. (C) 2018 Shenyang Pharmaceutical University. Published by Elsevier B.V.
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