Exploiting the preferential phagocytic uptake of nanoparticle-antigen conjugates for the effective treatment of autoimmunity

• Published in: Nanomedicine Vol. 40; p. 102481
• Main Authors: Sadanandan, Prashant, Payne, Natalie L., Sun, Guizhi, Ashokan, Anusha, Gowd, Siddaramana G., Lal, Arsha, Satheesh Kumar, Madathiparambil Kumaran, Pulakkat, Sreeranjini, Nair, Shantikumar V., Menon, Krishnakumar N., Bernard, Claude C.A., Koyakutty, Manzoor
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2022
• Subjects: Animals; Autoimmunity; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - pathology; Experimental autoimmune encephalomyelitis; Mice; Mice, Inbred C57BL; Mononuclear phagocytic system; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - pathology; Myelin oligodendrocyte glycoprotein; Myelin-Oligodendrocyte Glycoprotein - therapeutic use; Nanoparticles; Silica nanoparticles; Silica nanoparticles; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Mononuclear phagocytic system; Myelin oligodendrocyte glycoprotein
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2021.102481

Tolerance induction is central to the suppression of autoimmunity. Here, we engineered the preferential uptake of nano-conjugated autoantigens by spleen-resident macrophages to re-introduce self-tolerance and suppress autoimmunity. The brain autoantigen, myelin oligodendrocyte glycoprotein (MOG), was conjugated to 200 or 500 nm silica nanoparticles (SNP) and delivered to the spleen and liver-resident macrophages of experimental autoimmune encephalomyelitis (EAE) mice, used as a model of multiple sclerosis. MOG-SNP conjugates significantly reduced signs of EAE at a very low dose (50 μg) compared to the higher dose (>800 μg) of free-MOG. This was associated with reduced proliferation of splenocytes and pro-inflammatory cytokines secretion, decreased spinal cord inflammation, demyelination and axonal damage. Notably, biodegradable porous SNP showed an enhanced disease suppression assisted by elevated levels of regulatory T cells and programmed-death ligands (PD-L1/2) in splenic and lymph node cells. Our results demonstrate that targeting nano-conjugated autoantigens to tissue-resident macrophages in lymphoid organs can effectively suppress autoimmunity.
Specific delivery of auto-antigen loaded nanoparticles to tissue-resident macrophages in lymphoid organs is a novel method to elicit immuno-modulatory response in autoimmunity. We demonstrated this by using myelin oligodendrocyte glycoprotein (MOG) peptide conjugated porous silica nanoparticles (pSNP) in the Experimental Autoimmune Encephalomyelitis (EAE) model of multiple sclerosis. [Display omitted]