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 ππ 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 ππ interactions of the Phe co-monomer in the polypeptide block, with high potential as biocompatible nanocarriers for RNA interference.
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