CXCR4-targeted modular peptide carriers for efficient anti-VEGF siRNA delivery

Publication date: 30 December 2016 Source:International Journal of Pharmaceutics, Volume 515, Issues 1–2 Author(s): Anna Egorova, Anastasia Shubina, Dmitriy Sokolov, Sergey Selkov, Vladislav Baranov, Anton Kiselev The application of small interfering RNA (siRNA) for specific gene inhibition is a promising strategy in gene therapy treatments. The efficient cellular delivery of therapeutic siRNA is a critical step in RNA interference (RNAi) application. Highly efficient siRNA carriers should be developed for specific cellular uptake, stable RNA-complexes formation and intracellular RNA release. To study these features, we evaluated modular peptide carriers bearing CXCR4 targeting ligand for their ability to condense siRNA, facilitate endosomal escape and VEGFA gene silencing in CXCR4-expressing endothelial and glioblastoma cells. Peptide carriers were shown to condense and protect siRNA from RNAse degradation. Various N/P ratios were used for physicochemical characterization to optimize siRNA/peptide complexes for in vitro studies. On average, cytotoxicity of siRNA-polyplexes depended on cell type and was not higher than that of PEI/siRNA complexes. VEGFA gene knockdown was significantly improved with CXCR4-targeted carriers in contrast to nontargeted peptides. siRNA delivery by means of ligandconjugated carriers resulted in 2.5–3-fold decrease of VEGF expression in glioblastoma cells and in 1.5–2-fold decrease of VEGF expression in endothelial cells. Delivery of ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research