Identification of critical points in colloidal delivery systems for intravenous administration and intracellular delivery of nucleic acids as therapeutic agents (original) (raw)

The RNA-mediated gene-silencing technology, carried out by small interfering RNAs (siRNAs), has attracted a great deal of attention as novel promising therapeutic strategy in oncology. One of the common themes emerging from the studies on cell-specific delivery of siRNA is the need for optimizing the intracellular trafficking of the siRNA to elicit a silencing response. Polymer nanoparticles have become recognized as an efficiency strategy for oligonucleotide delivery to a specific cell population. Among these carriers, PLGA-co-PEG nanoparticles have attracted much attention since they are assumed to meet the criteria required for successful siRNA delivery: they are sufficiently small for efficient tissue penetration and cellular uptake and offer physical protection against RNase activity as well as a favorable colloidal stability. In this study the ability of a polymeric micelle based system for the targeting and delivery of a siRNA to breast cancer cells was proved using as model the siRNA against the Green Fluorescence Protein (GFP). The efficiencies observed during in vitro studies with a MDA-MB-436/GFP cell line confirmed the potential of this new delivery system but it needs further investigation.