title: Enhanced cellular uptake and gene silencing activity of siRNA molecules mediated by chitosan-derivative nanocomplexes.
abstract: The RNA interference (RNAi) constitutes a conservative mechanism in eukaryotic cells that induces silencing of target genes. In mammalians, the RNAi is triggered by siRNA (small interfering RNA) molecules. Due to its potential in silencing specific genes, the siRNA has been considered a potential alternative for the treatment of genetic and acquired diseases. However, the siRNA therapy has been limited by its low stability and rapid degradation in presence of nucleases, low cellular uptake, and immune response activation. In order to overcome these drawbacks, we propose the synthesis and characterization of non-viral delivery systems using chitosan derivatives to obtain siRNA complexes (polyplexes). The non-viral delivery systems synthesized included PEG-g-OCs (oligochitosan) and PEG-g-Cs (chitosan medium molecular weight). Both systems allowed the formation of siRNA polyplexes, increased the stability of siRNA in the presence of nucleases, enhanced cellular internalization, and showed low toxicity in the A549 cell line. Finally, the complexes obtained with the PEG-g-OCs system showed silencing activity in a GFP model in the cell line A549 in comparison with naked siRNA.
authors: Facultad de Farmacia, Universidad Autonoma del Estado de Morelos, Cuernavaca 62209, Mexico; Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, TX 78712-0120, United States.
authors: Diana
authors: D
authors: Guzman-Villanueva
authors: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, TX 78712-0120, United States.
authors: Ibrahim M
authors: IM
authors: El-Sherbiny
authors: Life Technologies, Austin, TX 78744, United States.
authors: Alexander V
authors: AV
authors: Vlassov
authors: Facultad de Farmacia, Universidad Autonoma del Estado de Morelos, Cuernavaca 62209, Mexico. Electronic address: dherrera@uaem.mx.
authors: Dea
authors: D
authors: Herrera-Ruiz
authors: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, TX 78712-0120, United States. Electronic address: hugh.smyth@austin.utexas.edu.
authors: Hugh D C
authors: HD
authors: Smyth
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D009844:Oligosaccharides; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D009844:Oligosaccharides; D034741:RNA, Small Interfering; C493484:oligochitosan; D002686:Chitin; D049452:Green Fluorescent Proteins; D048271:Chitosan
keywords: Chitosan; Chitosan (PubChem CID: 71853); Egg white lysozyme (PubChem CID: 71581463); Hydroxybenzotriazole (PubChem CID: 75771); Nanocomplexes; PEG; Phthalic anhydride (PubChem CID: 6811); Polymers; RNAi; siRNA