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Nanoparticle Platforms for Antigen-Specific Immune Tolerance.

ABSTRACT: Innovative approaches in nanoparticle design have facilitated the creation of new formulations of nanoparticles that are capable of selectively calibrating the immune response. These nanomaterials may be engineered to interact with specific cellular and molecular targets. Recent advancements in nanoparticle synthesis have enabled surface functionalization of particles that mimic the diversity of ligands on the cell surface. Platforms synthesized using these design principles, called "biomimetic" nanoparticles, have achieved increasingly sophisticated targeting specificity and cellular trafficking capabilities. This holds great promise for next generation therapies that seek to achieve immune tolerance. In this review, we discuss the importance of physical design parameters including size, shape, and biomimetic surface functionalization, on the biodistribution, safety and efficacy of biologic nanoparticles. We will also explore potential applications for immune tolerance for organ or stem cell transplantation.

SUBMITTER: Thorp EB

PROVIDER: S-EPMC7251028 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Nanoparticle Platforms for Antigen-Specific Immune Tolerance.

Thorp Edward B EB Boada Christian C Jarbath Clarens C Luo Xunrong X

Frontiers in immunology 20200520

Innovative approaches in nanoparticle design have facilitated the creation of new formulations of nanoparticles that are capable of selectively calibrating the immune response. These nanomaterials may be engineered to interact with specific cellular and molecular targets. Recent advancements in nanoparticle synthesis have enabled surface functionalization of particles that mimic the diversity of ligands on the cell surface. Platforms synthesized using these design principles, called "biomimetic" ...[more]

PMID: 32508829

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Project description: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-?, 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-? 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.

Dataset Information

Nanoparticle Platforms for Antigen-Specific Immune Tolerance.

Publications

Nanoparticle Platforms for Antigen-Specific Immune Tolerance.

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