Conjugation of Transforming Growth Factor Beta to Antigen-Loaded Poly(lactide- co-glycolide) Nanoparticles Enhances Efficiency of Antigen-Specific Tolerance.

Autor:	Casey LM; Department of Chemical Engineering , University of Michigan , 2300 Hayward Avenue , Ann Arbor , Michigan 48105 , United States., Pearson RM; Department of Biomedical Engineering , University of Michigan , 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard , Ann Arbor , Michigan 48109-2099 , United States.; Cour Pharmaceuticals, Northbrook , Illinois 60062 , United States., Hughes KR; Department of Biomedical Engineering , University of Michigan , 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard , Ann Arbor , Michigan 48109-2099 , United States., Liu JMH; Department of Biomedical Engineering , University of Michigan , 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard , Ann Arbor , Michigan 48109-2099 , United States., Rose JA; Department of Chemical Engineering , University of Michigan , 2300 Hayward Avenue , Ann Arbor , Michigan 48105 , United States., North MG; Department of Biomedical Engineering , University of Michigan , 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard , Ann Arbor , Michigan 48109-2099 , United States., Wang LZ; Department of Biomedical Engineering , University of Michigan , 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard , Ann Arbor , Michigan 48109-2099 , United States., Lei M; Department of Biomedical Engineering , University of Michigan , 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard , Ann Arbor , Michigan 48109-2099 , United States., Miller SD; Department of Microbiology-Immunology, Feinberg School of Medicine , Northwestern University , 6-713 Tarry Building, 303 East Chicago Avenue , Chicago , Illinois 60611 , United States.; The Robert H. Lurie Comprehensive Cancer Center of Northwestern University , Chicago , Illinois 60611 , United States., Shea LD; Department of Chemical Engineering , University of Michigan , 2300 Hayward Avenue , Ann Arbor , Michigan 48105 , United States.; Department of Biomedical Engineering , University of Michigan , 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard , Ann Arbor , Michigan 48109-2099 , United States.
Jazyk:	angličtina
Zdroj:	Bioconjugate chemistry [Bioconjug Chem] 2018 Mar 21; Vol. 29 (3), pp. 813-823. Date of Electronic Publication: 2017 Nov 30.
DOI:	10.1021/acs.bioconjchem.7b00624
Abstrakt:	Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v.) administration of poly(lactide- co-glycolide) nanoparticles (NPs) containing disease-relevant antigens (Ag-NPs) have demonstrated antigen (Ag)-specific immune tolerance in models of autoimmunity. However, subcutaneous (s.c.) delivery of Ag-NPs has not been effective. This investigation tested the hypothesis that codelivery of the immunomodulatory cytokine, transforming growth factor beta 1 (TGF-β), on Ag-NPs would modulate the immune response to Ag-NPs and improve the efficiency of tolerance induction. TGF-β was coupled to the surface of Ag-NPs such that the loadings of Ag and TGF-β were independently tunable. The particles demonstrated bioactive delivery of Ag and TGF-β in vitro by reducing the inflammatory phenotype of bone marrow-derived dendritic cells and inducing regulatory T cells in a coculture system. Using an in vivo mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis, TGF-β codelivery on Ag-NPs resulted in improved efficacy at lower doses by i.v. administration and significantly reduced disease severity by s.c. administration. This study demonstrates that the codelivery of immunomodulatory cytokines on Ag-NPs may enhance the efficacy of Ag-specific tolerance therapies by programming Ag presenting cells for more efficient tolerance induction.
Databáze:	MEDLINE
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