Successful achievement of RNA interference in therapeutic applications requires safe and efficient vectors for siRNA delivery.
In the present study, we demonstrate that a triethanolamine (TEA)-core PAMAM dendrimer of generation 5 (G(5)) is able to deliver sticky siRNAs bearing complementary A(n)/T(n) 3'-overhangs effectively to a prostate cancer model in vitro and in vivo and produce potent gene silencing of the heat shock protein 27, leading to a notable anticancer effect. The complementary A(n)/T(n) (n = 5 or 7) overhangs characteristic of these sticky siRNA molecules help the siRNA molecules self-assemble into "gene-like" longer double-stranded RNAs thus endowing a low generation dendrimer such as G(5) with greater delivery capacity. In addition, the A(n)/T(n) (n = 5 or 7) overhangs act as protruding molecular arms that allow the siRNA molecule to enwrap the dendrimer and promote a better interaction and stronger binding, ultimately contributing toward the improved delivery activity of G(5). Consequently, the low generation dendrimer G(5) in combination with sticky siRNA therapeutics may constitute a promising gene silencing-based approach for combating castration-resistant prostate tumors or other cancers and diseases, for which no effective treatment currently exists.
Written by:
Liu X, Liu C, Laurini E, Posocco P, Pricl S, Qu F, Rocchi P, Peng L. Are you the author?
Département de Chimie, Centre Interdisciplinaire de Nanoscience de Marseille, CNRS UMR 7325, Aix-Marseille Université , 163 avenue de Luminy, 13288 Marseille, France.
Reference: Mol Pharm. 2012 Jan 20. [Epub ahead of print]
PubMed Abstract
PMID: 22208617
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