Nano-Targeted Delivery of Immune Therapeutics in type 1 Diabetes.

Immune therapeutics hold great promise in the treatment of type 1 diabetes (T1D). Nonetheless, their progress has been hampered by limited efficacy, equipoise, or issues of safety. To address this, we developed a novel and specific nanodelivery platform for T1D that targets high endothelial venules (HEVs) presented in the pancreatic lymph nodes (PLNs) and pancreas. Our data indicate that the pancreata of non-obese diabetic (NOD) mice and patients with T1D are unique in their expression of newly formed HEVs. We encapsulated anti-CD3 mAb in PLGA-PEG nanoparticles (NPs), the surfaces of which were conjugated with MECA79 mAb that recognizes HEVs. Targeted delivery of these NPs improved accumulation of anti-CD3 mAb in both the PLNs and pancreata of NOD mice. Treatment of hyperglycemic NOD mice with MECA79-anti-CD3-NPs resulted in significant reversal of T1D compared to those that were untreated, treated with empty NPs, or provided free anti-CD3. This effect was 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 sum, 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. This article is protected by copyright. All rights reserved.