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Accepted (AM)Open Access (License Unspecified), Open
Journal article
PEGylation enables subcutaneously administered nanoparticles to induce antigen-specific immune tolerance
Journal of controlled release, v 331
10 Mar 2021
PMID: 33450320
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The development of nanomaterials to induce antigen-specific immune tolerance has shown promise for treating autoimmune diseases. While PEGylation has been widely used to reduce host immune responses to nanomaterials, its tolerogenic potential has not been reported. Here, we report for the first time that a subcutaneous injection of PEGylated poly(lactide-co-glycolide) (PLGA) nanoparticles containing auto-antigen peptide MOG35–55 without any tolerogenic drugs is sufficient to dramatically ameliorate symptoms after disease onset in an antigen-specific manner in a mouse model of multiple sclerosis. Neither free MOG35–55 nor particles without PEG exhibit this efficacy. Interestingly, mechanistic studies indicate that PEGylation of nanoparticles does not reduce dendritic cell activation through direct nanoparticle-cell interactions. Instead, PEGylated nanoparticles induce lower complement activation, neutrophil recruitment, and co-stimulatory molecule expression on dendritic cells around the injection sitecompared to non-PEGylated PLGA nanoparticles, creating a more tolerogenic microenvironment in vivo. We further demonstrate that the locally recruited dendritic cells traffic to lymphoid organs to induce T cell tolerance. These results highlight the critical role of surface properties of nanomaterials in inducing immune tolerance via subcutaneous administration.
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Details
- Title
- PEGylation enables subcutaneously administered nanoparticles to induce antigen-specific immune tolerance
- Creators
- Peter Y. Li - Drexel UniversityFrank Bearoff - Drexel UniversityPu Zhu - Drexel UniversityZhiyuan Fan - Drexel UniversityYucheng Zhu - Drexel UniversityMingyue Fan - Drexel UniversityLaura Cort - Drexel UniversityTaku Kambayashi - University of PennsylvaniaElizabeth P. Blankenhorn - Drexel UniversityHao Cheng - Drexel University
- Publication Details
- Journal of controlled release, v 331
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; School of Biomedical Engineering, Science, and Health Systems; Materials Science and Engineering
- Web of Science ID
- WOS:000626476700013
- Scopus ID
- 2-s2.0-85099657685
- Other Identifier
- 991019168181704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary
- Pharmacology & Pharmacy