聚乙二醇化
体内
化学
肽
小干扰RNA
体外
PEG比率
内化
生物物理学
聚乙二醇
药物输送
生物化学
转染
药理学
细胞
生物
经济
有机化学
生物技术
基因
财务
作者
Gudrun Aldrian,Anaïs Vaissière,Karidia Konate,Quentin Seisel,Éric Vivès,F. Fernandez,Véronique Viguier,Coralie Genevois,Franck Couillaud,Hélène Déméné,Dina Aggad,Aurélie Covinhes,Stéphanie Barrère-Lemaire,Sébastien Deshayes,Prisca Boisguérin
标识
DOI:10.1016/j.jconrel.2017.04.012
摘要
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.
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