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

Autor: Javanmardi, Sanaz, Tamaddon, Ali Mohammad, Aghamaali, Mahmoud Reza, Ghahramani, Ladan, Abolmaali, Samira Sadat
Předmět:
Zdroj: Asian Journal of Pharmaceutical Sciences; Jan2020, Vol. 15 Issue 1, p69-82, 14p
Abstrakt: 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 pk a have been introduced for cellular delivery of Anti-miR-21. The synthesis was characterized using 1 H 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index