Article (Scientific journals)
PEGylated and Functionalized Aliphatic Polycarbonate Polyplex Nanoparticles for Intravenous Administration of HDAC5 siRNA in Cancer Therapy
Frère, Antoine; Baroni, Alexandra; Hendrick, Elodie et al.
2017In ACS Applied Materials and Interfaces, 25 (9(3)), p. 2181-2195
Peer Reviewed verified by ORBi
 

Files


Full Text
PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy
Publisher postprint (2.59 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
siRNA; polyplex nanoparticles; intravenous administration; aliphatic polycarbonat; polyethylene glycol; protein corona
Abstract :
[en] Guanidine and morpholine functionalized aliphatic polycarbonate polymers are able to efficiently deliver 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 zeta 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.
Research center :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Giga-Signal Transduction - ULiège
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Frère, Antoine ;  Université de Liège > Département de pharmacie > Pharmacie galénique
Baroni, Alexandra
Hendrick, Elodie ;  Université de Liège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Delvigne, Anne Sophie
Orange, François
Peulen, Olivier  ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Dakwar, Georges
Diricq, Jerome
Dubois, Philippe
Evrard, Brigitte  ;  Université de Liège > Département de pharmacie > Pharmacie galénique
Remaut, Katrien
Braeckmans, Kevin
De Smedt, Stefaan
Laloy, Julie
Dogne, Jean Michel
Feller, Georges ;  Université de Liège > Département des sciences de la vie > Laboratoire de biochimie
Mespouilles, Laetitia
Mottet, Denis ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Piel, Géraldine ;  Université de Liège > Département de pharmacie > Pharmacie galénique
More authors (9 more) Less
Language :
English
Title :
PEGylated and Functionalized Aliphatic Polycarbonate Polyplex Nanoparticles for Intravenous Administration of HDAC5 siRNA in Cancer Therapy
Publication date :
2017
Journal title :
ACS Applied Materials and Interfaces
ISSN :
1944-8244
eISSN :
1944-8252
Publisher :
American Chemical Society, United States - District of Columbia
Volume :
25
Issue :
9(3)
Pages :
2181-2195
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 11 January 2017

Statistics


Number of views
159 (28 by ULiège)
Number of downloads
8 (8 by ULiège)

Scopus citations®
 
20
Scopus citations®
without self-citations
17
OpenCitations
 
17

Bibliography


Similar publications



Contact ORBi