Design of biodegradable nanoparticles to modulate phenotypes of antigen-presenting cells for antigen-specific treatment of autoimmune disease
Biomaterials, ISSN: 0142-9612, Vol: 222, Page: 119432
2019
- 55Citations
- 82Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations55
- Citation Indexes54
- 54
- CrossRef40
- Patent Family Citations1
- Patent Families1
- Captures82
- Readers82
- 82
Article Description
Current therapeutic options for autoimmune diseases, such as multiple sclerosis (MS), often require lifelong treatment with immunosuppressive drugs, yet strategies for antigen-specific immunomodulation are emerging. Biodegradable particles loaded with disease-specific antigen, either alone or with immunomodulators, have been reported to ameliorate disease. Herein, we hypothesized that the carrier could impact polarization of the immune cells that associate with particles and the subsequent disease progression. Single injection of three polymeric carriers, 50:50 poly (DL-lactide-co-glycolide) (PLG) with two molecular weights (Low, High) and poly (DL-lactide) (PLA), loaded with the disease-specific antigen, proteolipid protein (PLP 139-151 ), were investigated for the ability to attenuate clinical scores in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. At a low particle dose, mice treated with PLA-based particles had significantly lower clinical scores at the chronic stage of the disease over 200 days post immunization, while neither PLG-based particles nor OVA control particles reduced the clinical scores. Compared to PLG-based particles, PLA-based particles were largely associated with Kupffer cells and liver sinusoidal endothelial cells, which had a reduced co-stimulatory molecule expression that correlated with a reduction of CD4 + T-cell populations in the central nervous system. Delivery of PLA-based particles encapsulated with higher levels of PLP 139-151 at a reduced dose were able to completely ameliorate EAE over 200 days along with inhibition of Th1 and Th17 polarization. Collectively, our study demonstrates that the carrier properties and antigen loading determine phenotypes of immune cells in the peripheral organs, influencing the amelioration of both acute and chronic stages of autoimmunity.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0142961219305319; http://dx.doi.org/10.1016/j.biomaterials.2019.119432; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85071425286&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/31480002; https://linkinghub.elsevier.com/retrieve/pii/S0142961219305319; https://dx.doi.org/10.1016/j.biomaterials.2019.119432
Elsevier BV
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