Table 1. Nanoparticles investigated for antigen-specific immune regulation delivering protein or peptide antigens.

Indication	Particle type	Antigen	Important finding	Refere nce
EAE	Ag-coupled PLGA and PS	PLP139-151; PLP178-191; MBP35-55	MARCO scavenger receptor mediated tolerance induction	[64]
EAE	Ag-coupled PLGA	PLP139-151; PLP178-191	Lower negative charge on particles resulted in improved efficacy	[74]
EAE	Ag-coupled PLGA	OVA323-339; PLP139-151	Increased Ag conjugation and particle concentration enhanced Ag presentation and reduced co-stimulatory expression	[154]
EAE	Ag-encapsulated PLGA	OVA323-339; PLP139-151; PLP178-191	Tolerance induction was not completely dependent on the spleen	[70]
EAE	Ag-polymer conjugate PLGA	OVA323-339; PLP139-151; PLP178-191	Modular Ag loading, negligible burst release, tolerance induction to multiple epitopes	[94]
EAE	Ag-encapsulated PLGA and IL-10 encapsulated PLGA	MOG35-55	Subcutaneous prophylactic administration reduced clinical disease. Co-administration of IL-10 PLGA was necessary to suppress disease	[67]
EAE	Ag and rapamycin co-encapsulated PLGA/PLA-PEG	PLP139-151	Significantly reduced clinical disease score when Ag co-encapsulated with rapamycin.	[65]
EAE	Poly(maleic anhydride-alt-1-octadecene)-coated superparamagnet ic iron oxide nanocrystals	MBPAC-1-9 (4Tyr); MOG35-55	Ag delivery to LSECs by particles induced Ag-specific Tregs and suppressed clinical disease	[69]
EAE	Ag and ITE-loaded	MOG35-55; PLP139-151;	Co-encapsulation of ITE with particles expanded Tregs	[66]
	PEGylated gold	PLP178-191	and suppressed clinical disease
EAE	Peptide-MHCII complex-conjugated iron oxide	N/A	Tolerance mediated by expansion of Ag-specific TR1-like cells and suppressive regulatory B cells	[133]
Diabetes	Peptide-MHCI complex-conjugated iron oxide	N/A	Expanded CD8+ T cells with regulatory potential but conventional memory-like phenotype	[149]
Diabetes	Peptide-MHCII complex-conjugated iron oxide	N/A	Tolerance mediated by expansion of Ag-specific TR1-like cells and suppressive regulatory B cells	[133]
Glomerular	Ag-coupled latex	OVA	Tolerance in the liver is	[97]
nephritis			dependent on KCs in a noninflammatory microenvironment
Collagen	Ag-encapsulated	CII	Oral administration of	[155]
induced	PLGA		particles suppressed arthritis
arthritis			symptoms
Collagen	Peptide-MHCII	N/A	Tolerance mediated by	[133]
induced	complex-		expansion of Ag-specific
arthritis	conjugated iron oxide		TR1-like cells and suppressive regulatory B cells
Proteoglyc	Ag-encapsulated	Hsp 70-	Intranasal delivery of	[156]
an induced	PLGA and	peptide	particles suppressed arthritis
arthritis	PLGA-TMC	mB29a	symptoms
Islet	Ag-coupled	Donor cell	Full MHC-mismatched	[71]
transplant	PLGA	lysate	murine allogeneic transplantation was achieved in 20% of recipients and improved to 60% with short course rapamycin
Bone	Ag-encapsulated	Dby, Uty	Delivery of CD4 Dby epitope	[49]
marrow	PLGA		prevented transplant
transplant			rejection and delivery of CD8 epitope Uty did not induce tolerance
Hemophilia	Ag-encapsulated PLGA/PLA-PEG	Factor VIII	Significantly reduced antibody formation when Ag co-encapsulated with rapamycin.	[65]
Hemophilia	Ag-conjugated liposomes	Factor VIII	Suppression of antibody responses and prevented bleeding when delivered with CD22 ligand	[119]
Anti-drug antibody	Ag-conjugated liposomes	OVA; MOG1-120	Suppression of antibody responses when delivered with CD22 ligand	[119]
Anti-drug antibody	Soluble Ag and rapamycin-encapsulated PLGA/PLA-PEG	OVA; OVA323-339; adalimumab; pegsiticase	Delivery of rapamycin in particles and Ag within 1 day of particle administration was necessary to suppress antibody responses	[118]
Allergy	Ag-encapsulated PLGA/PLA-PEG	OVA; OVA323-339	Significantly reduced antibody formation when Ag co-encapsulated with rapamycin.	[65]
Allergy	Liposomes	OVA	Suppression of antibody responses when delivered with CD22 ligand	[119]
Allergy	Ag-encapsulated PLGA	Bet v 1	Subcutaneous administration of particles modulated Th2 response	[157]
Allergy	Ag-encapsulated PLGA	OE109-130	Intranasal administration of particles suppressed IgE and IgG1 production but increased IgG2a	[158]
Allergy	Ag-encapsulated PLGA	OVA	Inhibited Th2 responses in models of allergic airway inflammation	[73]

PLGA (poly(lactide-co-glycolide)); PS (polystyrene); PLA-PEG (polylactide-poly(ethylene glycol)); TMC (trimethyl chitosan); LSEC (liver sinusoidal endothelial cell); KC (Kupffer cell); OVA (Ovalbumin); PLP (proteolipid protein); MOG (myelin oligodendrocyte protein); MBP (Myelin basic protein); CII (type II collagen); Bet v 1 (Birch pollen allergen); OE (Olive allergen); ITE (2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester)