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PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy

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Abstract
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 (PEG(750) or PEG(2000)) 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.
Keywords
siRNA, polyplex nanoparticles, intravenous administration, aliphatic polycarbonate, polyethylene glycol, protein corona, HISTONE DEACETYLASE INHIBITORS, RING-OPENING POLYMERIZATION, SYSTEMIC GENE DELIVERY, DRUG-DELIVERY, CELLULAR UPTAKE, PROTEIN CORONA, BIOLOGICAL-FLUIDS, CELLS, DESIGN, BARRIERS

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MLA
Frère, Antoine et al. “PEGylated and Functionalized Aliphatic Polycarbonate Polyplex Nanoparticles for Intravenous Administration of HDAC5 siRNA in Cancer Therapy.” ACS APPLIED MATERIALS & INTERFACES 9.3 (2017): 2181–2195. Print.
APA
Frère, A., Baroni, A., Hendrick, E., Delvigne, A.-S., Orange, F., Peulen, O., Dakwar, G., et al. (2017). PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy. ACS APPLIED MATERIALS & INTERFACES, 9(3), 2181–2195.
Chicago author-date
Frère, Antoine, Alexandra Baroni, Elodie Hendrick, Anne-Sophie Delvigne, François Orange, Olivier Peulen, George Dakwar, et al. 2017. “PEGylated and Functionalized Aliphatic Polycarbonate Polyplex Nanoparticles for Intravenous Administration of HDAC5 siRNA in Cancer Therapy.” Acs Applied Materials & Interfaces 9 (3): 2181–2195.
Chicago author-date (all authors)
Frère, Antoine, Alexandra Baroni, Elodie Hendrick, Anne-Sophie Delvigne, François Orange, Olivier Peulen, George Dakwar, Jérôme Diricq, Philippe Dubois, Brigitte Evrard, Katrien Remaut, Kevin Braeckmans, Stefaan De Smedt, Julie Laloy, Jean-Michel Dogné, Georges Feller, Laetitia Mespouille, Denis Mottet, and Géraldine Piel. 2017. “PEGylated and Functionalized Aliphatic Polycarbonate Polyplex Nanoparticles for Intravenous Administration of HDAC5 siRNA in Cancer Therapy.” Acs Applied Materials & Interfaces 9 (3): 2181–2195.
Vancouver
1.
Frère A, Baroni A, Hendrick E, Delvigne A-S, Orange F, Peulen O, et al. PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy. ACS APPLIED MATERIALS & INTERFACES. 2017;9(3):2181–95.
IEEE
[1]
A. Frère et al., “PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy,” ACS APPLIED MATERIALS & INTERFACES, vol. 9, no. 3, pp. 2181–2195, 2017.
@article{8520080,
  abstract     = {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 (PEG(750) or PEG(2000)) 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.},
  author       = {Frère, Antoine and Baroni, Alexandra and Hendrick, Elodie and Delvigne, Anne-Sophie and Orange, François and Peulen, Olivier and Dakwar, George and Diricq, Jérôme and Dubois, Philippe and Evrard, Brigitte and Remaut, Katrien and Braeckmans, Kevin and De Smedt, Stefaan and Laloy, Julie and Dogné, Jean-Michel and Feller, Georges and Mespouille, Laetitia and Mottet, Denis and Piel, Géraldine},
  issn         = {1944-8244},
  journal      = {ACS APPLIED MATERIALS & INTERFACES},
  keywords     = {siRNA,polyplex nanoparticles,intravenous administration,aliphatic polycarbonate,polyethylene glycol,protein corona,HISTONE DEACETYLASE INHIBITORS,RING-OPENING POLYMERIZATION,SYSTEMIC GENE DELIVERY,DRUG-DELIVERY,CELLULAR UPTAKE,PROTEIN CORONA,BIOLOGICAL-FLUIDS,CELLS,DESIGN,BARRIERS},
  language     = {eng},
  number       = {3},
  pages        = {2181--2195},
  title        = {PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy},
  url          = {http://dx.doi.org/10.1021/acsami.6b15064},
  volume       = {9},
  year         = {2017},
}

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