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PEGylation rate influences peptide-based nanoparticles mediated siRNA delivery in vitro and in vivo

J Control Release. 2017 Jun 28;256:79-91. doi: 10.1016/j.jconrel.2017.04.012. Epub 2017 Apr 12.PEGylation rate influences peptide-based nanoparticles mediated siRNA delivery in vitro and in vivo.Aldrian G1, Vaissière A2, Konate K2, Seisel Q2, Vivès E2, Fernandez F3, Viguier V3, Genevois C4, Couillaud F4, Démèné H5, Aggad D6, Covinhes A7, Barrère-Lemaire S7, Deshayes S2, Boisguerin P8.Author information1Sys2Diag, CNRS UMR 9005/ALCEDIAG, 1682 Rue de la Valsière, 34184 Montpellier Cedex 4, France.2Centre de Recherche de Biologie cellulaire de Montpellier, CNRS UMR 5237, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.3Microscopie Electronique et Analytique, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.4EA 7435 IMOTION (Imagerie moléculaire et thérapies innovantes en oncologie), Université de Bordeaux, 146 rue Leo Saignat, 33076 Bordeaux, France.5Centre de Biochimie Structurale, CNRS UMR 5048, Inserm U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France.6Institut des Biomolécules Max Mousseron, CNRS UMR 5247, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France.7Institut de Génomique Fonctionnelle, CNRS UMR 5203, Inserm U661, Université de Montpellier, 141 Rue de la Cardonille, 34094 Montpellier Cedex 5, France.; Laboratory of Excellence Ion Channel Science and Therapeutics, F-06560 Valbonne.8Centre de Recherche de Biologie cellulaire de Montpellier, CNRS UMR 5237, 1919 Route de Mende, 34293 Montpellier Cedex 5, France. Electronic address: [email protected] interfering RNAs (siRNAs) present a strong therapeutic potential because of their ability to inhibit the expression of any desired protein. Recently, we developed the retro-inverso amphipathic RICK peptide as novel non-covalent siRNA carrier. This peptide is able to form nanoparticles (NPs) by self-assembling with the siRNA resulting in the fully siRNA protection based on its protease resistant peptide sequence. With regard to an in vivo application, we investigated here the influence of the polyethylene glycol (PEG) grafting to RICK NPs on their in vitro and in vivo siRNA delivery properties. A detailed structural study shows that PEGylation did not alter the NP formation (only decrease in zeta potential) regardless of the used PEGylation rates. Compared to the native RICK:siRNA NPs, low PEGylation rates (≤20%) of the NPs did not influence their cellular internalization capacity as well as their knock-down specificity (over-expressed or endogenous system) in vitro. Because the behavior of PEGylated NPs could differ in their in vivo application, we analyzed the repartition of fluorescent labeled NPs injected at the one-cell stage in zebrafish embryos as well as their pharmacokinetic (PK) profile after administration to mice. After an intra-cardiac injection of the PEGylated NPs, we could clearly determine that 20% PEG-RICK NPs reduce significantly liver and kidney accumulation. NPs with 20% PEGylation constitutes a modular, easy-to-handle drug delivery system which could be adapted to other types of functional moieties to develop safe and biocompatible delivery systems for the clinical application of RNAi-based cancer therapeutics.Copyright © 2017 Elsevier B.V. All rights reserved.KEYWORDS: Cell penetrating peptides; Gene knock-down; Nanoparticle; PEGylation; Retro-inverso; siRNA deliveryPMID: 28411182 DOI: 10.1016/j.jconrel.2017.04.012 [Indexed for MEDLINE] ShareMeSH terms, SubstancesMeSH termsAnimalsCell-Penetrating Peptides/administration & dosage*Cell-Penetrating Peptides/chemistryCysteine/administration & dosageCysteine/chemistryEmbryo, NonmammalianLuciferases/geneticsMaleMice, Inbred C57BLNanoparticles/administration & dosage*Nanoparticles/chemistryPolyethylene Glycols/administration & dosage*Polyethylene Glycols/chemistryRNA, Small Interfering/administration & dosage*RNA, Small Interfering/chemistryReceptor-Interacting Protein Serine-Threonine Kinase 2/administration & dosage*Receptor-Interacting Protein Serine-Threonine Kinase 2/chemistrySurface PropertiesZebrafishSubstancesCell-Penetrating PeptidesRNA, Small InterferingPolyethylene GlycolsLuciferasesReceptor-Interacting Protein Serine-Threonine Kinase 2CysteineLinkOut - more resourcesFull Text SourcesElsevier ScienceOvid Technologies, Inc.Molecular Biology DatabasesZFINMiscellaneousCYSTEINE - Hazardous Substances Data BankNCI CPTAC Assay Portal

تاثیر pegylation بر سنتز نانو ذرات مبتنی بر پپتید با واسطه پپتید وابسته به پپتید در شرایط in vitro و in vivo

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