PMID- 25796349 OWN - NLM STAT- MEDLINE DCOM- 20160215 LR - 20181202 IS - 1873-3441 (Electronic) IS - 0939-6411 (Linking) VI - 92 DP - 2015 May TI - Versatile polyion complex micelles for peptide and siRNA vectorization to engineer tolerogenic dendritic cells. PG - 216-27 LID - S0939-6411(15)00146-0 [pii] LID - 10.1016/j.ejpb.2015.03.013 [doi] AB - Dendritic cells (DCs) are professional antigen-presenting cells that play a critical role in maintaining the balance between immunity and tolerance and, as such are a promising immunotherapy tool to induce immunity or to restore tolerance. The main challenge to harness the tolerogenic properties of DCs is to preserve their immature phenotype. We recently developed polyion complex micelles, formulated with double hydrophilic block copolymers of poly(methacrylic acid) and poly(ethylene oxide) blocks and able to entrap therapeutic molecules, which did not induce DC maturation. In the current study, the intrinsic destabilizing membrane properties of the polymers were used to optimize endosomal escape property of the micelles in order to propose various strategies to restore tolerance. On the first hand, we showed that high molecular weight (Mw) copolymer-based micelles were efficient to favor the release of the micelle-entrapped peptide into the endosomes, and thus to improve peptide presentation by immature (i) DCs. On the second hand, we put in evidence that low Mw copolymer-based micelles were able to favor the cytosolic release of micelle-entrapped small interfering RNAs, dampening the DCs immunogenicity. Therefore, we demonstrate the versatile use of polyionic complex micelles to preserve tolerogenic properties of DCs. Altogether, our results underscored the potential of such micelle-loaded iDCs as a therapeutic tool to restore tolerance in autoimmune diseases. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Mebarek, Naila AU - Mebarek N AD - Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe MACS, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France. FAU - Vicente, Rita AU - Vicente R AD - Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe MACS, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France; Inserm, U 1183, Universite Montpellier, CHU St-Eloi, 80 avenue Augustin Fliche, 34298 Montpellier Cedex 5, France. FAU - Aubert-Pouessel, Anne AU - Aubert-Pouessel A AD - Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe MACS, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France. Electronic address: aaubert@univ-montp1.fr. FAU - Quentin, Julie AU - Quentin J AD - Inserm, U 1183, Universite Montpellier, CHU St-Eloi, 80 avenue Augustin Fliche, 34298 Montpellier Cedex 5, France. FAU - Mausset-Bonnefont, Anne-Laure AU - Mausset-Bonnefont AL AD - Inserm, U 1183, Universite Montpellier, CHU St-Eloi, 80 avenue Augustin Fliche, 34298 Montpellier Cedex 5, France. FAU - Devoisselle, Jean-Marie AU - Devoisselle JM AD - Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe MACS, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France. FAU - Jorgensen, Christian AU - Jorgensen C AD - Inserm, U 1183, Universite Montpellier, CHU St-Eloi, 80 avenue Augustin Fliche, 34298 Montpellier Cedex 5, France. FAU - Begu, Sylvie AU - Begu S AD - Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe MACS, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France. FAU - Louis-Plence, Pascale AU - Louis-Plence P AD - Inserm, U 1183, Universite Montpellier, CHU St-Eloi, 80 avenue Augustin Fliche, 34298 Montpellier Cedex 5, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150318 PL - Netherlands TA - Eur J Pharm Biopharm JT - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JID - 9109778 RN - 0 (Micelles) RN - 0 (Peptides) RN - 0 (Polymers) RN - 0 (Polymethacrylic Acids) RN - 0 (RNA, Small Interfering) RN - 25087-26-7 (polymethacrylic acid) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Dendritic Cells/*immunology MH - Endosomes/metabolism MH - Hydrophobic and Hydrophilic Interactions MH - Immune Tolerance MH - Micelles MH - Molecular Weight MH - Peptides/*administration & dosage MH - Polyethylene Glycols/chemistry MH - Polymers/*chemistry MH - Polymethacrylic Acids/chemistry MH - RNA, Small Interfering/*administration & dosage OTO - NOTNLM OT - Antigen presentation OT - Dendritic cells OT - Endosomal escape OT - Gene silencing OT - Polyion complex micelles EDAT- 2015/03/23 06:00 MHDA- 2016/02/16 06:00 CRDT- 2015/03/23 06:00 PHST- 2014/07/10 00:00 [received] PHST- 2015/03/06 00:00 [revised] PHST- 2015/03/10 00:00 [accepted] PHST- 2015/03/23 06:00 [entrez] PHST- 2015/03/23 06:00 [pubmed] PHST- 2016/02/16 06:00 [medline] AID - S0939-6411(15)00146-0 [pii] AID - 10.1016/j.ejpb.2015.03.013 [doi] PST - ppublish SO - Eur J Pharm Biopharm. 2015 May;92:216-27. doi: 10.1016/j.ejpb.2015.03.013. Epub 2015 Mar 18.