AYDINLIOGLU, Esra; ABDELGHANI, Mona; LE FER, Gaëlle; VAN HEST, Jan C. M.; SANDRE, Olivier; LECOMMANDOUX, Sébastien

doi:10.1002/macp.202200306

Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 3 LCPO : Polymer Self-Assembly & Life Sciences

ABDELGHANI, Mona
Eindhoven University of Technology [Eindhoven] [TU/e]

LE FER, Gaëlle
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 3 LCPO : Polymer Self-Assembly & Life Sciences
Unité Matériaux et Transformations - UMR 8207 [UMET]

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Ce document a été publié dans

Macromolecular Chemistry and Physics. 2022-11-30p. 202200306

Résumé en anglais

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 were synthesized. N-carboxyanhydride (NCA) ring opening polymerization (ROP) was 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, was interpreted by π-π stacking hydrophobic interactions between the Phe residues, playing the role of “physical cross-linking”. These PICsomes were successfully loaded with siRNA directed against firefly luciferase enzyme expression. They also exhibit minimal cell cytotoxicity while superior silencing efficacy was 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 enabled 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.< Réduire

Mots clés

poly(L-glutamic acid)

poly(L-lysine)

poly(L-phenylalanine)

N-carboxyanhydride (NCA)

ring opening polymerization (ROP)

circular dichroism

small interfering RNA (siRNA)

polyionic complex (PIC) vesicles

Mots clés en anglais

PEO-b-poly(amino acids) block copolymers

PICsomes

siRNAsomes

URI

https://oskar-bordeaux.fr/handle/20.500.12278/170447

DOI

http://dx.doi.org/10.1002/macp.202200306

Unités de recherche

Laboratoire de Chimie des Polymères Organiques (LCPO) - UMR 5629

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Robust Polyion Complex Vesicles (PICsomes) based on PEO‐ b ‐Poly(Amino Acid) Copolymers Combining Electrostatic and Hydrophobic Interaction: Formation, siRNA Loading and Intracellular Delivery