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.
Boudier
Ariane
A
Institut Charles Gerhardt Montpellier, UMR 5253 CNRS/ENSCM/UM2/UM1, 8 rue de l'Ecole Normale, F-34296 Montpellier Cedex 5, France.
Aubert-Pouëssel
Anne
A
Louis-Plence
Pascale
P
Gérardin
Corine
C
Jorgensen
Christian
C
Devoisselle
Jean-Marie
JM
Bégu
Sylvie
S
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