RRC ID 59703
Author Liu Q, Wang X, Liu X, Kumar S, Gochman G, Ji Y, Liao YP, Chang CH, Situ W, Lu J, Jiang J, Mei KC, Meng H, Xia T, Nel AE.
Title Use of Polymeric Nanoparticle Platform Targeting the Liver To Induce Treg-Mediated Antigen-Specific Immune Tolerance in a Pulmonary Allergen Sensitization Model.
Journal ACS Nano
Abstract Nanoparticles (NPs) can be used to accomplish antigen-specific immune tolerance in allergic and autoimmune disease. The available options for custom-designing tolerogenic NPs include the use of nanocarriers that introduce antigens into natural tolerogenic environments, such as the liver, where antigen presentation promotes tolerance to self- or foreign antigens. Here, we demonstrate the engineering of a biodegradable polymeric poly(lactic- co-glycolic acid) (PLGA) nanocarrier for the selective delivery of the murine allergen, ovalbumin (OVA), to the liver. This was accomplished by developing a series of NPs in the 200-300 nm size range as well as decorating particle surfaces with ligands that target scavenger and mannose receptors on liver sinusoidal endothelial cells (LSECs). LSECs represent a major antigen-presenting cell type in the liver capable of generating regulatory T-cells (Tregs).  In vitro exposure of LSECs to NPOVA induced abundant TGF-β, IL-4, and IL-10 production, which was further increased by surface ligands. Animal experiments showed that, in the chosen size range, NPOVA was almost exclusively delivered to the liver, where the colocalization of fluorescent-labeled particles with LSECs could be seen to increase by surface ligand decoration. Moreover, prophylactic treatment with NPOVA in OVA-sensitized and challenged animals (aerosolized inhalation) could be seen to significantly suppress anti-OVA IgE responses, airway eosinophilia, and TH2 cytokine production in the bronchoalveolar lavage fluid. The suppression of allergic airway inflammation was further enhanced by attachment of surface ligands, particularly for particles decorated with the ApoB peptide, which induced high levels of TGF-β production in the lung along with the appearance of Foxp3+ Tregs. The ApoB-peptide-coated NPs could also interfere in allergic airway inflammation when delivered postsensitization. The significance of these findings is that liver and LSEC targeting PLGA NPs could be used for therapy of allergic airway disease, in addition to the potential of using their tolerogenic effects for other disease applications.
Volume 13(4)
Pages 4778-4794
Published 2019-4-23
DOI 10.1021/acsnano.9b01444
PMID 30964276
PMC PMC6506187
MeSH Allergens / administration & dosage* Allergens / immunology Animals Antigen Presentation Drug Carriers / chemistry Drug Delivery Systems Immune Tolerance* Liver / immunology* Mice, Inbred BALB C Mice, Inbred C57BL Nanoparticles / chemistry Ovalbumin / administration & dosage* Ovalbumin / immunology Polylactic Acid-Polyglycolic Acid Copolymer / chemistry* T-Lymphocytes, Regulatory / immunology*
IF 13.903
Times Cited 7
Human and Animal Cells KUP5(RCB4627)