Nanotargeted Delivery of Immune Therapeutics in Type 1 Diabetes

Bibliographische Detailangaben
Veröffentlicht in:	Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 40 vom: 01. Okt., Seite e2300812
1. Verfasser:	Jung, Sungwook (VerfasserIn)
Weitere Verfasser:	Ben Nasr, Moufida, Bahmani, Baharak, Usuelli, Vera, Zhao, Jing, Sabiu, Gianmarco, Seelam, Andy Joe, Naini, Said Movahedi, Balasubramanian, Hari Baskar, Park, Youngrong, Li, Xiaofei, Khalefa, Salma Ayman, Kasinath, Vivek, Williams, MacKenzie D, Rachid, Ousama, Haik, Yousef, Tsokos, George C, Wasserfall, Clive H, Atkinson, Mark A, Bromberg, Jonathan S, Tao, Wei, Fiorina, Paolo, Abdi, Reza
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2023
Zugriff auf das übergeordnete Werk:	Advanced materials (Deerfield Beach, Fla.)
Schlagworte:	Journal Article drug delivery high endothelial venules nanomedicine targeted therapy type 1 diabetes

Beschreibung
Zusammenfassung:	© 2023 Wiley-VCH GmbH. 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
Beschreibung:	Date Completed 05.10.2023 Date Revised 04.10.2024 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-4095
DOI:	10.1002/adma.202300812