The control of dendritic cell maturation by pH-sensitive polyion complex micelles

被引:41
作者
Boudier, Ariane [1 ]
Aubert-Pouessel, Anne [1 ]
Louis-Plence, Pascale [2 ,3 ]
Gerardin, Corine [1 ]
Jorgensen, Christian [2 ,3 ,4 ]
Devoisselle, Jean-Marie [1 ]
Begu, Sylvie [1 ]
机构
[1] CNRS, Inst Charles Gerhardt Montpellier, ENSCM,UMR 5253, UM2,UM1, F-34296 Montpellier 5, France
[2] INSERM, U 844, F-34295 Montpellier 5, France
[3] Univ Montpellier 1, F-34967 Montpellier 2, France
[4] CHU Montpellier, Hop Lapeyronie, Unite Clin Immuno Rhumatol Therapeut Malad Articu, F-34295 Montpellier, France
关键词
Polyion complex micelles; pH-sensitivity; Dendritic cell; Maturation control; Immunotherapy; ACID) BLOCK-COPOLYMER; REGULATORY T-CELLS; DRUG-DELIVERY; GENE DELIVERY; POLY(L-LYSINE); EXPANSION; VEHICLES; PYRENE; CORE;
D O I
10.1016/j.biomaterials.2008.09.033
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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-POE5000)/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. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:233 / 241
页数:9
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