聚乙二醇化
体内
生物物理学
材料科学
体外
体内分布
小干扰RNA
聚乙二醇
PEG比率
转染
生物化学
化学
生物
生物技术
财务
基因
经济
作者
Antoine Frère,Alexandra Baroni,Elodie Hendrick,Anne Sophie Delvigne,François Orange,Olivier Peulen,George R. Dakwar,Jérôme Diricq,Philippe Dubois,Brigitte Évrard,Katrien Remaut,Kevin Braeckmans,Stefaan C. De Smedt,Julie Laloy,Jean Michel Dogné,Georges Feller,Laetitia Mespouille,Denis Mottet,Géraldine Piel
标识
DOI:10.1021/acsami.6b15064
摘要
Guanidine and morpholine functionalized aliphatic polycarbonate polymers are able to deliver efficiently histone deacetylase 5 (HDAC5) siRNA into the cytoplasm of cancer cells in vitro leading to a decrease of cell proliferation were previously developed. To allow these biodegradable and biocompatible polyplex nanoparticles to overcome the extracellular barriers and be effective in vivo after an intravenous injection, polyethylene glycol chains (PEG750 or PEG2000) were grafted on the polymer structure. These nanoparticles showed an average size of about 150 nm and a slightly positive ζ-potential with complete siRNA complexation. Behavior of PEGylated and non-PEGylated polyplexes were investigated in the presence of serum, in terms of siRNA complexation (fluorescence correlation spectroscopy), size (dynamic light scattering and single-particle tracking), interaction with proteins (isothermal titration calorimetry) and cellular uptake. Surprisingly, both PEGylated and non-PEGylated formulations presented relatively good behavior in the presence of fetal bovine serum (FBS). Hemocompatibility tests showed no effect of these polyplexes on hemolysis and coagulation. In vivo biodistribution in mice was performed and showed a better siRNA accumulation at the tumor site for PEGylated polyplexes. However, cellular uptake in protein-rich conditions showed that PEGylated polyplex lost their ability to interact with biological membranes and enter into cells, showing the importance to perform in vitro investigations in physiological conditions closed to in vivo situation. In vitro, the efficiency of PEGylated nanoparticles decreases compared to non-PEGylated particles, leading to the loss of the antiproliferative effect on cancer cells.
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