The control of dendritic cell maturation by pH-sensitive polyion complex micelles.
Double-hydrophilic block copolymer micelles were designed as vectors for ex vivo dendritic cell engineering to improve the delivery of therapeutic molecules in such immune cells. Polymethacrylic acid-b-polyethylene oxide (PMAA(2100)-b-POE(5000))/poly-L-lysine micelles were optimised and showed a hydrodynamic diameter of 30 nm with a peculiar core organised with hydrogen bonds as well as hydrophobic domains. The micelles proved high stability in physiological conditions (pH and ionic strength) and were also able to disassemble under acidic conditions mimicking acidic endolysosomes. The efficient endocytosis of the optimised micelles tested on bone marrow-derived dendritic cells was monitored by fluorescence-activated cell sorting and microscopy analysis. Finally, the micelle biocompatibility permitted a complete control of the dendritic cell-maturation process widening the therapeutical potential of such engineered dendritic cells for cancer vaccines as well as for immunomodulation in autoimmune diseases.
Institut Charles Gerhardt Montpellier, UMR 5253 CNRS/ENSCM/UM2/UM1, 8 rue de l'Ecole Normale, F-34296 Montpellier Cedex 5, France.
Ariane
A
Boudier
Anne
A
Aubert-Pouëssel
Pascale
P
Louis-Plence
Corine
C
Gérardin
Christian
C
Jorgensen
Jean-Marie
JM
Devoisselle
Sylvie
S
Bégu
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D008856:Microscopy, Fluorescence; D011092:Polyethylene Glycols / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D011109:Polymethacrylic Acids / Q000737:chemistry*
D008823:Micelles; D011108:Polymers; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D011107:Polylysine; D011092:Polyethylene Glycols