PUBLICATION
PEGylation rate influences peptide-based nanoparticles mediated siRNA delivery in vitro and in vivo
- Authors
- Aldrian, G., Vaissière, A., Konate, K., Seisel, Q., Vivès, E., Fernandez, F., Viguier, V., Genevois, C., Couillaud, F., Démèné, H., Aggad, D., Covinhes, A., Barrère-Lemaire, S., Deshayes, S., Boisguerin, P.
- ID
- ZDB-PUB-170416-2
- Date
- 2017
- Source
- Journal of controlled release : official journal of the Controlled Release Society 256: 79-91 (Journal)
- Registered Authors
- Keywords
- Cell penetrating peptides, Gene knock-down, Nanoparticle, PEGylation, Retro-inverso, siRNA delivery
- MeSH Terms
-
- Animals
- Cell-Penetrating Peptides/administration & dosage*
- Cell-Penetrating Peptides/chemistry
- Cysteine/administration & dosage
- Cysteine/chemistry
- Embryo, Nonmammalian
- Luciferases/genetics
- Male
- Mice, Inbred C57BL
- Nanoparticles/administration & dosage*
- Nanoparticles/chemistry
- Polyethylene Glycols/administration & dosage*
- Polyethylene Glycols/chemistry
- RNA, Small Interfering/administration & dosage*
- RNA, Small Interfering/chemistry
- Receptor-Interacting Protein Serine-Threonine Kinase 2/administration & dosage*
- Receptor-Interacting Protein Serine-Threonine Kinase 2/chemistry
- Surface Properties
- Zebrafish
- PubMed
- 28411182 Full text @ J. Control Release
Citation
Aldrian, G., Vaissière, A., Konate, K., Seisel, Q., Vivès, E., Fernandez, F., Viguier, V., Genevois, C., Couillaud, F., Démèné, H., Aggad, D., Covinhes, A., Barrère-Lemaire, S., Deshayes, S., Boisguerin, P. (2017) PEGylation rate influences peptide-based nanoparticles mediated siRNA delivery in vitro and in vivo. Journal of controlled release : official journal of the Controlled Release Society. 256:79-91.
Abstract
Small 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping