Controlled Delivery of Single or Multiple Antigens in Tolerogenic Nanoparticles Using Peptide-Polymer Bioconjugates.

Autor:	Pearson RM; Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109-2099, USA., Casey LM; Department of Chemical Engineering, University of Michigan, 2300 Hayward Ave., Ann Arbor, MI 48105, USA., Hughes KR; Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109-2099, USA., Wang LZ; Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109-2099, USA., North MG; Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109-2099, USA., Getts DR; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 6-713 Tarry Building, 303 E. Chicago Avenue, Chicago, IL 60611, USA., Miller SD; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 6-713 Tarry Building, 303 E. Chicago Avenue, Chicago, IL 60611, USA; Chemistry of Life Processes Institute (CLP), Northwestern University, Evanston, IL 60208, USA; The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA. Electronic address: s-d-miller@northwestern.edu., Shea LD; Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109-2099, USA; Department of Chemical Engineering, University of Michigan, 2300 Hayward Ave., Ann Arbor, MI 48105, USA. Electronic address: ldshea@umich.edu.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2017 Jul 05; Vol. 25 (7), pp. 1655-1664. Date of Electronic Publication: 2017 May 05.
DOI:	10.1016/j.ymthe.2017.04.015
Abstrakt:	Polymeric nanoparticles (NPs) have demonstrated their potential to induce antigen (Ag)-specific immunological tolerance in multiple immune models and are at various stages of commercial development. Association of Ag with NPs is typically achieved through surface coupling or encapsulation methods. However, these methods have limitations that include high polydispersity, uncontrollable Ag loading and release, and possible immunogenicity. Here, using antigenic peptides conjugated to poly(lactide-co-glycolide), we developed Ag-polymer conjugate NPs (acNPs) with modular loading of single or multiple Ags, negligible burst release, and minimally exposed surface Ag. Tolerogenic responses of acNPs were studied in vitro to decouple the role of NP size, concentration, and Ag loading on regulatory T cell (Treg) induction. CD4 + CD25 + Foxp3 + Treg induction was dependent on NP size, but CD25 expression of CD4 + T cells was not. NP concentration and Ag loading could be modulated to achieve maximal levels of Treg induction. In relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE), a murine model of multiple sclerosis, acNPs were effective in inhibiting disease induced by a single peptide or multiple peptides. The acNPs provide a simple, modular, and well-defined platform, and the NP physicochemical properties offer potential to design and answer complex mechanistic questions surrounding NP-induced tolerance. (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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