Redox-Sensitive, PEG-Shielded Carboxymethyl PEI Nanogels Silencing MicroRNA-21, Sensitizes Resistant Ovarian Cancer Cells to Cisplatin

Publication date: Available online 1 December 2018Source: Asian Journal of Pharmaceutical SciencesAuthor(s): Sanaz Javanmardi, Ali Mohammad Tamaddon, Mahmoud Reza Aghamaali, Ladan Ghahramani, Samira Sadat AbolmaaliAbstractA 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 1H-NMR, FTIR, TNBS, potentiometric titration, particle size and ΞΆ 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-CMPEI-ss mediated microRNA delivery can be considered as a novel strategy for ovarian cancer therapy.Graphical ...
Source: Asian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research