Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions: Formation, siRNA Loading and Intracellular Delivery

Esra Aydinlioglu; Mona Abdelghani; Gaëlle Le Fer; Jan C.M. van Hest; Olivier Sandre; Sébastien Lecommandoux

doi:10.1002/macp.202200306

Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions: Formation, siRNA Loading and Intracellular Delivery

Esra Aydinlioglu, Mona Abdelghani, Gaëlle Le Fer, Jan C.M. van Hest, Olivier Sandre (Corresponding author), Sébastien Lecommandoux (Corresponding author)

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Two pairs of oppositely charged PEO-b-poly(amino acid) copolymers with neutral poly(ethylene oxide) block and polypeptide block composed of the hydrophobic l-phenylalanine (Phe) amino acid mixed with either negative l-glutamic acid (Glu) or positive l-lysine (Lys) units are synthesized. N-carboxyanhydride (NCA) ring opening polymerization is performed with either PEO₄₆-NH₂ or PEO₁₁₄-NH₂ macroinitiators, leading respectively to PEO₄₆-b-P(Glu₁₀₀-co-Phe₆₅) and PEO₄₆-b-P(Lys₁₀₀-co-Phe₆₅), and PEO₁₁₄-b-P(Glu₆₀-co-Phe₄₀) and PEO₁₁₄-b-P(Lys₆₀-co-Phe₄₀). Polyion complexes (PIC) formed at near charge equilibrium led to vesicle formation (PICsomes), as shown by DLS, zetametry, and TEM. The good stability of PICsomes, even in high salinity media, is interpreted by π π stacking hydrophobic interactions between the Phe residues, playing the role of “physical cross-linking”. These PICsomes are successfully loaded with small interfering ribonucleic acid (siRNA) directed against firefly luciferase enzyme expression. They also exhibit minimal cell cytotoxicity while superior silencing efficacy is shown by cell bioluminescence assay as compared to free siRNA and a standard lipofectamine-siRNA complex. As such, self-assembly of oppositely charged PEO-b-poly(amino acids) block copolymers enables forming PICsomes of high stability thanks to π π interactions of the Phe co-monomer in the polypeptide block, with high potential as biocompatible nanocarriers for RNA interference.

Originele taal-2	Engels
Artikelnummer	2200306
Aantal pagina's	11
Tijdschrift	Macromolecular Chemistry and Physics
Volume	224
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1002/macp.202200306
Status	Gepubliceerd - 10 jan. 2023

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© 2022 The Authors. Macromolecular Chemistry and Physics published by Wiley-VCH GmbH.

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This work was supported by the European Union's Horizon 2020 research and innovation programme Marie Sklodowska-Curie Innovative Training Networks (ITN) Nanomed, under grant No. 676 137. The authors are grateful to Dr. Anne-Laure Wirotius for1H NMR training, Amelie Wax for GPC analysis, Dr Christophe Schatz and Quentin Larger for help with light scattering experiments and discussions. Transmission electron microscopy (TEM) was performed at the Bordeaux Imaging Center, a service unit of the CNRS-INSERM and Bordeaux University, member of the national infrastructure France BioImaging; the authors are also grateful to Sabrina Lacomme for the TEM training sessions. This work was supported by the European Union's Horizon 2020 research and innovation programme Marie Sklodowska‐Curie Innovative Training Networks (ITN) Nanomed, under grant No. 676 137. The authors are grateful to Dr. Anne‐Laure Wirotius forH NMR training, Amelie Wax for GPC analysis, Dr Christophe Schatz and Quentin Larger for help with light scattering experiments and discussions. Transmission electron microscopy (TEM) was performed at the Bordeaux Imaging Center, a service unit of the CNRS‐INSERM and Bordeaux University, member of the national infrastructure France BioImaging; the authors are also grateful to Sabrina Lacomme for the TEM training sessions. 1

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Aydinlioglu, E., Abdelghani, M., Le Fer, G., van Hest, J. C. M., Sandre, O., & Lecommandoux, S. (2023). Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions: Formation, siRNA Loading and Intracellular Delivery. Macromolecular Chemistry and Physics, 224(1), Artikel 2200306. https://doi.org/10.1002/macp.202200306

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title = "Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions: Formation, siRNA Loading and Intracellular Delivery",

abstract = "Two pairs of oppositely charged PEO-b-poly(amino acid) copolymers with neutral poly(ethylene oxide) block and polypeptide block composed of the hydrophobic l-phenylalanine (Phe) amino acid mixed with either negative l-glutamic acid (Glu) or positive l-lysine (Lys) units are synthesized. N-carboxyanhydride (NCA) ring opening polymerization is performed with either PEO46-NH2 or PEO114-NH2 macroinitiators, leading respectively to PEO46-b-P(Glu100-co-Phe65) and PEO46-b-P(Lys100-co-Phe65), and PEO114-b-P(Glu60-co-Phe40) and PEO114-b-P(Lys60-co-Phe40). Polyion complexes (PIC) formed at near charge equilibrium led to vesicle formation (PICsomes), as shown by DLS, zetametry, and TEM. The good stability of PICsomes, even in high salinity media, is interpreted by π π stacking hydrophobic interactions between the Phe residues, playing the role of “physical cross-linking”. These PICsomes are successfully loaded with small interfering ribonucleic acid (siRNA) directed against firefly luciferase enzyme expression. They also exhibit minimal cell cytotoxicity while superior silencing efficacy is shown by cell bioluminescence assay as compared to free siRNA and a standard lipofectamine-siRNA complex. As such, self-assembly of oppositely charged PEO-b-poly(amino acids) block copolymers enables forming PICsomes of high stability thanks to π π interactions of the Phe co-monomer in the polypeptide block, with high potential as biocompatible nanocarriers for RNA interference.",

keywords = "PEO-b-poly(amino acids) block copolymers, polyion complexes, polypeptides, ring opening polymerization, small interfering RNA",

author = "Esra Aydinlioglu and Mona Abdelghani and {Le Fer}, Ga{\"e}lle and {van Hest}, {Jan C.M.} and Olivier Sandre and S{\'e}bastien Lecommandoux",

note = "Funding Information: This work was supported by the European Union's Horizon 2020 research and innovation programme Marie Sklodowska-Curie Innovative Training Networks (ITN) Nanomed, under grant No. 676 137. The authors are grateful to Dr. Anne-Laure Wirotius for1H NMR training, Amelie Wax for GPC analysis, Dr Christophe Schatz and Quentin Larger for help with light scattering experiments and discussions. Transmission electron microscopy (TEM) was performed at the Bordeaux Imaging Center, a service unit of the CNRS-INSERM and Bordeaux University, member of the national infrastructure France BioImaging; the authors are also grateful to Sabrina Lacomme for the TEM training sessions. ",

year = "2023",

month = jan,

day = "10",

doi = "10.1002/macp.202200306",

language = "English",

volume = "224",

journal = "Macromolecular Chemistry and Physics",

issn = "1022-1352",

publisher = "Wiley-VCH Verlag",

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Aydinlioglu, E, Abdelghani, M, Le Fer, G, van Hest, JCM, Sandre, O & Lecommandoux, S 2023, 'Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions: Formation, siRNA Loading and Intracellular Delivery', Macromolecular Chemistry and Physics, vol. 224, nr. 1, 2200306. https://doi.org/10.1002/macp.202200306

Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions: Formation, siRNA Loading and Intracellular Delivery. / Aydinlioglu, Esra; Abdelghani, Mona; Le Fer, Gaëlle et al.
In: Macromolecular Chemistry and Physics, Vol. 224, Nr. 1, 2200306, 10.01.2023.

Onderzoeksoutput: Bijdrage aan tijdschrift › Tijdschriftartikel › Academic › peer review

TY - JOUR

T1 - Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions

T2 - Formation, siRNA Loading and Intracellular Delivery

AU - Aydinlioglu, Esra

AU - Abdelghani, Mona

AU - Le Fer, Gaëlle

AU - van Hest, Jan C.M.

AU - Sandre, Olivier

AU - Lecommandoux, Sébastien

N1 - Funding Information: This work was supported by the European Union's Horizon 2020 research and innovation programme Marie Sklodowska-Curie Innovative Training Networks (ITN) Nanomed, under grant No. 676 137. The authors are grateful to Dr. Anne-Laure Wirotius for1H NMR training, Amelie Wax for GPC analysis, Dr Christophe Schatz and Quentin Larger for help with light scattering experiments and discussions. Transmission electron microscopy (TEM) was performed at the Bordeaux Imaging Center, a service unit of the CNRS-INSERM and Bordeaux University, member of the national infrastructure France BioImaging; the authors are also grateful to Sabrina Lacomme for the TEM training sessions.

PY - 2023/1/10

Y1 - 2023/1/10

N2 - Two pairs of oppositely charged PEO-b-poly(amino acid) copolymers with neutral poly(ethylene oxide) block and polypeptide block composed of the hydrophobic l-phenylalanine (Phe) amino acid mixed with either negative l-glutamic acid (Glu) or positive l-lysine (Lys) units are synthesized. N-carboxyanhydride (NCA) ring opening polymerization is performed with either PEO46-NH2 or PEO114-NH2 macroinitiators, leading respectively to PEO46-b-P(Glu100-co-Phe65) and PEO46-b-P(Lys100-co-Phe65), and PEO114-b-P(Glu60-co-Phe40) and PEO114-b-P(Lys60-co-Phe40). Polyion complexes (PIC) formed at near charge equilibrium led to vesicle formation (PICsomes), as shown by DLS, zetametry, and TEM. The good stability of PICsomes, even in high salinity media, is interpreted by π π stacking hydrophobic interactions between the Phe residues, playing the role of “physical cross-linking”. These PICsomes are successfully loaded with small interfering ribonucleic acid (siRNA) directed against firefly luciferase enzyme expression. They also exhibit minimal cell cytotoxicity while superior silencing efficacy is shown by cell bioluminescence assay as compared to free siRNA and a standard lipofectamine-siRNA complex. As such, self-assembly of oppositely charged PEO-b-poly(amino acids) block copolymers enables forming PICsomes of high stability thanks to π π interactions of the Phe co-monomer in the polypeptide block, with high potential as biocompatible nanocarriers for RNA interference.

AB - Two pairs of oppositely charged PEO-b-poly(amino acid) copolymers with neutral poly(ethylene oxide) block and polypeptide block composed of the hydrophobic l-phenylalanine (Phe) amino acid mixed with either negative l-glutamic acid (Glu) or positive l-lysine (Lys) units are synthesized. N-carboxyanhydride (NCA) ring opening polymerization is performed with either PEO46-NH2 or PEO114-NH2 macroinitiators, leading respectively to PEO46-b-P(Glu100-co-Phe65) and PEO46-b-P(Lys100-co-Phe65), and PEO114-b-P(Glu60-co-Phe40) and PEO114-b-P(Lys60-co-Phe40). Polyion complexes (PIC) formed at near charge equilibrium led to vesicle formation (PICsomes), as shown by DLS, zetametry, and TEM. The good stability of PICsomes, even in high salinity media, is interpreted by π π stacking hydrophobic interactions between the Phe residues, playing the role of “physical cross-linking”. These PICsomes are successfully loaded with small interfering ribonucleic acid (siRNA) directed against firefly luciferase enzyme expression. They also exhibit minimal cell cytotoxicity while superior silencing efficacy is shown by cell bioluminescence assay as compared to free siRNA and a standard lipofectamine-siRNA complex. As such, self-assembly of oppositely charged PEO-b-poly(amino acids) block copolymers enables forming PICsomes of high stability thanks to π π interactions of the Phe co-monomer in the polypeptide block, with high potential as biocompatible nanocarriers for RNA interference.

KW - PEO-b-poly(amino acids) block copolymers

KW - polyion complexes

KW - polypeptides

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DO - 10.1002/macp.202200306

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Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions: Formation, siRNA Loading and Intracellular Delivery

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