A retro-inverso cell-penetrating peptide for siRNA delivery

Journal of Nanobiotechnology

Research

Carole Jourdan¹  Anaïs Vaissière¹  Quentin Seisel¹  Prisca Boisguerin¹  Karidia Konate¹  Sébastien Deshayes¹  Anthony Telmar¹  Mattias F. Lindberg¹  Coralie Genevois²  Franck Couillaud²  Frédéric Fernandez³  Véronique Viguier³  Gudrun Aldrian⁴ 

[1] Centre de Recherche de Biologie cellulaire de Montpellier, UMR 5237 CNRS, 1919 Route de Mende, 34293, Montpellier, France;EA 7435 IMOTION (Imagerie moléculaire et thérapies innovantes en oncologie), Université de Bordeaux, 146 rue Leo Saignat, 33076, Bordeaux, France;Microscopie Électronique et Analytique, Université de Montpellier, Place Eugène Bataillon, 34095, Montpellier, France;Sys2Diag, UMR 9005-CNRS/ALCEDIAG, 1682 Rue de la Valsiere, 34184, Montpellier, France;

关键词: Enantiomer;    -Amino acids;    Retro-inverso;    siRNA delivery;    Cell penetrating peptides;    Nanoparticle;    Gene knock-down;    Cancer;   

DOI  :  10.1186/s12951-017-0269-2

 received in 2016-11-04, accepted in 2017-04-17,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundSmall interfering RNAs (siRNAs) are powerful tools to control gene expression. However, due to their poor cellular permeability and stability, their therapeutic development requires a specific delivery system. Among them, cell-penetrating peptides (CPP) have been shown to transfer efficiently siRNA inside the cells. Recently we developed amphipathic peptides able to self-assemble with siRNAs as peptide-based nanoparticles and to transfect them into cells. However, despite the great potential of these drug delivery systems, most of them display a low resistance to proteases.ResultsHere, we report the development and characterization of a new CPP named RICK corresponding to the retro-inverso form of the CADY-K peptide. We show that RICK conserves the main biophysical features of its L-parental homologue and keeps the ability to associate with siRNA in stable peptide-based nanoparticles. Moreover the RICK:siRNA self-assembly prevents siRNA degradation and induces inhibition of gene expression.ConclusionsThis new approach consists in a promising strategy for future in vivo application, especially for targeted anticancer treatment (e.g. knock-down of cell cycle proteins).Graphical abstractRICK-based nanoparticles: RICK peptides and siRNA self-assemble in peptide-based nanoparticles to penetrate into the cells and to induce target protein knock-down.

【 授权许可】

CC BY   
© The Author(s) 2017