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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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.

Original languageEnglish
Article number2200306
Number of pages11
JournalMacromolecular Chemistry and Physics
Volume224
Issue number1
DOIs
Publication statusPublished - 10 Jan 2023

Bibliographical 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.

Funding

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

Keywords

  • PEO-b-poly(amino acids) block copolymers
  • polyion complexes
  • polypeptides
  • ring opening polymerization
  • small interfering RNA

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