title: Poly(I:C) coated PLGA microparticles induce dendritic cell maturation.
abstract: Microparticles from poly(D,L-lactic-co-glycolic acid) [PLGA] are of steadily rising interest for the delivery of antigens to immune cells and the induction of a long-lasting immune response for vaccination or immunological tumor therapy. However, if the desired vaccine contains only weak antigens and fails to activate the antigen presenting cells (APC), the opposite effect, i.e., the induction of immunotolerance may be observed. Therefore, it was the aim of this study to show the ability of protein loaded PLGA microparticles to additionally carry a specific, surface-coated maturation signal to human dendritic cells (DC), i.e., the most potent APC. Polyinosine-polycytidylic acid [poly(I:C)], a ligand of Toll-like receptor (TLR) 3, was efficiently bound either in a single layer or a multilayer attempt to the surface of diethylaminoethyl dextran modified PLGA microparticles. These particles were effectively phagocytized by DC ex vivo and induced a maturation similar to that achieved with a cytokine cocktail or higher concentrations of soluble poly(I:C). In conclusion, the concept of surface coating of biodegradable microparticles with selected TLR ligands might successfully be used in DC-based cell therapies for cancer or in vaccination trials to induce DC maturation and specifically amplify the immunological response to encapsulated antigens.
authors.affiliation: Department of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany. christian.wischke@berlin.de
authors.forename: Christian
authors.initials: C
authors.lastname: Wischke
authors.forename: Julian
authors.initials: J
authors.lastname: Zimmermann
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wessinger
authors.forename: Andreas
authors.initials: A
authors.lastname: Schendler
authors.forename: Hans-Hubert
authors.initials: HH
authors.lastname: Borchert
authors.forename: J Hinrich
authors.initials: JH
authors.lastname: Peters
authors.forename: Thomas
authors.initials: T
authors.lastname: Nesselhut
authors.forename: Dirk R
authors.initials: DR
authors.lastname: Lorenzen
mesh_terms: D002478:Cells, Cultured; D003637:DEAE-Dextran / Q000737:chemistry; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008024:Ligands; D008863:Microspheres; D010587:Phagocytosis; D011070:Poly I-C / Q000008:administration & dosage* / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D008024:Ligands; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003637:DEAE-Dextran; D011070:Poly I-C