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

Antoine Frère, Alexandra Baroni, Elodie Hendrick, Anne Sophie Delvigne, Francois Orange, Olivier Peulen, George R. Dakwar, Jérome Diricq, Philippe Dubois, Brigitte Evrard, Katrien Remaut, Kevin Braeckmans, Stefaan C. De Smedt, Julie Laloy, Jean Michel Dogné, Georges Feller, Laetitia Mespouille, Denis Mottet, Géraldine Piel

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

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 -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.

langueAnglais
Pages2181-2195
Nombre de pages15
journalACS Applied Materials and Interfaces
Volume9
Numéro3
Les DOIs
étatPublié - 25 janv. 2017

Empreinte digitale

Polycarbonates
Polyethylene glycols
Nanoparticles
Histone Deacetylases
polycarbonate
Small Interfering RNA
Complexation
Cells
Proteins
Polymers
Biological membranes
Cell proliferation
Calorimetry
Dynamic light scattering
Coagulation
Titration
Tumors
Fluorescence
Spectroscopy
Guanidine

mots-clés

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    Frère, Antoine ; Baroni, Alexandra ; Hendrick, Elodie ; Delvigne, Anne Sophie ; Orange, Francois ; Peulen, Olivier ; Dakwar, George R. ; Diricq, Jérome ; Dubois, Philippe ; Evrard, Brigitte ; Remaut, Katrien ; Braeckmans, Kevin ; De Smedt, Stefaan C. ; Laloy, Julie ; Dogné, Jean Michel ; Feller, Georges ; Mespouille, Laetitia ; Mottet, Denis ; Piel, Géraldine. / PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy. Dans: ACS Applied Materials and Interfaces. 2017 ; Vol 9, Numéro 3. p. 2181-2195
    @article{dfc94075f4764765936267079ea1cf01,
    title = "PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy",
    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 (PEG750 or PEG2000) were grafted on the polymer structure. These nanoparticles showed an average size of about 150 nm and a slightly positive -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 = "Aliphatic polycarbonate, Intravenous administration, Polyethylene glycol, Polyplex nanoparticles, Protein corona, siRNA",
    author = "Antoine Fr\{`e}re and Alexandra Baroni and Elodie Hendrick and Delvigne, {Anne Sophie} and Francois Orange and Olivier Peulen and Dakwar, {George R.} and J\{'e}rome Diricq and Philippe Dubois and Brigitte Evrard and Katrien Remaut and Kevin Braeckmans and {De Smedt}, {Stefaan C.} and Julie Laloy and Dogn\{'e}, {Jean Michel} and Georges Feller and Laetitia Mespouille and Denis Mottet and G\{'e}raldine Piel",
    year = "2017",
    month = "1",
    day = "25",
    doi = "10.1021/acsami.6b15064",
    language = "English",
    volume = "9",
    pages = "2181--2195",
    journal = "ACS Applied Materials and Interfaces",
    issn = "1944-8244",
    publisher = "American Chemical Society",
    number = "3",

    }

    Frère, A, Baroni, A, Hendrick, E, Delvigne, AS, Orange, F, Peulen, O, Dakwar, GR, Diricq, J, Dubois, P, Evrard, B, Remaut, K, Braeckmans, K, De Smedt, SC, Laloy, J, Dogné, JM, Feller, G, Mespouille, L, Mottet, D & Piel, G 2017, 'PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy' ACS Applied Materials and Interfaces, VOL 9, Numéro 3, p. 2181-2195. DOI: 10.1021/acsami.6b15064

    PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy. / Frère, Antoine; Baroni, Alexandra; Hendrick, Elodie; Delvigne, Anne Sophie; Orange, Francois; Peulen, Olivier; Dakwar, George R.; Diricq, Jérome; Dubois, Philippe; Evrard, Brigitte; Remaut, Katrien; Braeckmans, Kevin; De Smedt, Stefaan C.; Laloy, Julie; Dogné, Jean Michel; Feller, Georges; Mespouille, Laetitia; Mottet, Denis; Piel, Géraldine.

    Dans: ACS Applied Materials and Interfaces, Vol 9, Numéro 3, 25.01.2017, p. 2181-2195.

    Résultats de recherche: Contribution à un journal/une revueArticle

    TY - JOUR

    T1 - PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDAC5 siRNA in cancer therapy

    AU - Frère,Antoine

    AU - Baroni,Alexandra

    AU - Hendrick,Elodie

    AU - Delvigne,Anne Sophie

    AU - Orange,Francois

    AU - Peulen,Olivier

    AU - Dakwar,George R.

    AU - Diricq,Jérome

    AU - Dubois,Philippe

    AU - Evrard,Brigitte

    AU - Remaut,Katrien

    AU - Braeckmans,Kevin

    AU - De Smedt,Stefaan C.

    AU - Laloy,Julie

    AU - Dogné,Jean Michel

    AU - Feller,Georges

    AU - Mespouille,Laetitia

    AU - Mottet,Denis

    AU - Piel,Géraldine

    PY - 2017/1/25

    Y1 - 2017/1/25

    N2 - 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 -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.

    AB - 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 -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.

    KW - Aliphatic polycarbonate

    KW - Intravenous administration

    KW - Polyethylene glycol

    KW - Polyplex nanoparticles

    KW - Protein corona

    KW - siRNA

    UR - http://www.scopus.com/inward/record.url?scp=85011043647&partnerID=8YFLogxK

    U2 - 10.1021/acsami.6b15064

    DO - 10.1021/acsami.6b15064

    M3 - Article

    VL - 9

    SP - 2181

    EP - 2195

    JO - ACS Applied Materials and Interfaces

    T2 - ACS Applied Materials and Interfaces

    JF - ACS Applied Materials and Interfaces

    SN - 1944-8244

    IS - 3

    ER -