Redox-sensitive, PEG-shielded carboxymethyl PEI nanogels silencing MicroRNA-21, sensitizes resistant ovarian cancer cells to cisplatin

摘要

cqvip:A series of branched polyethylenimine(PEI) modifications including PEGylation(PEG2 k-PEI) for steric shielding, redox-sensitive crosslinking for synthesis PEG2 k-PEI-ss nanogels and subsequent carboxymethylation(PEG2 k-CMPEI-ss) for modulation of the polymer pk a have been introduced for cellular delivery of Anti-mi R-21. The synthesis was characterized using 1 H NMR, FTIR, TNBS, potentiometric titration, particle size and ζ potential. Loading of Anti-mi R-21 at various N/P ratios was investigated by gel retardation, ethidium bromide dye exclusion, heparin sulfate competition and DNase I digestion experiments. The mi R-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 PEG2 k-CMPEI-ss was well suited for delivery of Anti-mi R-21 in terms of nucleic acid loading, preservation against extracellular matrix and nucleases and sequence-specific silencing of mi RNA-21 in vitro. Moreover, it has been demonstrated that pre-treating cells with Anti-mi R-21 loaded nanogels can sensitize them to cis-Pt even at non-toxic concentraions. The results indicate that PEG2 k-CMPEIss mediated micro RNA delivery can be considered as a novel strategy for ovarian cancer therapy.