4.8 Article

Nanotargeted Delivery of Immune Therapeutics in Type 1 Diabetes

Journal

ADVANCED MATERIALS
Volume -, Issue -, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202300812

Keywords

drug delivery; high endothelial venules; nanomedicine; targeted therapy; type 1 diabetes

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A novel and specific nanodelivery platform targeting high endothelial venules (HEVs) in pancreatic lymph nodes (PLNs) and pancreas is developed to address the limited efficacy, equipoise, or safety issues of immune therapeutics in treating type 1 diabetes (T1D). By encapsulating anti-CD3 mAb in poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles (NPs) conjugated with MECA79 mAb, the targeted delivery of these NPs improves the accumulation of anti-CD3 mAb in both PLNs and pancreas of nonobese diabetic (NOD) mice. Treatment with MECA79-anti-CD3-NPs significantly reverses T1D in hyperglycemic NOD mice by reducing T effector cell populations and pro-inflammatory cytokine production in PLNs.
Immune therapeutics holds great promise in the treatment of type 1 diabetes (T1D). Nonetheless, their progress is hampered by limited efficacy, equipoise, or issues of safety. To address this, a novel and specific nanodelivery platform for T1D that targets high endothelial venules (HEVs) presented in the pancreatic lymph nodes (PLNs) and pancreas is developed. Data indicate that the pancreata of nonobese diabetic (NOD) mice and patients with T1D are unique in their expression of newly formed HEVs. Anti-CD3 mAb is encapsulated in poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles (NPs), the surfaces of which are conjugated with MECA79 mAb that recognizes HEVs. Targeted delivery of these NPs improves accumulation of anti-CD3 mAb in both the PLNs and pancreata of NOD mice. Treatment of hyperglycemic NOD mice with MECA79-anti-CD3-NPs results in significant reversal of T1D compared to those that are untreated, treated with empty NPs, or provided free anti-CD3. This effect is associated with a significant reduction of T effector cell populations in the PLNs and a decreased production of pro-inflammatory cytokine in the mice treated with MECA79-anti-CD3-NPs. In summary, HEV-targeted therapeutics may be used as a means by which immune therapeutics can be delivered to PLNs and pancreata to suppress autoimmune diabetes effectively.

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