TY - JOUR
T1 - Nanotargeted Delivery of Immune Therapeutics in Type 1 Diabetes
AU - Jung, Sungwook
AU - Ben Nasr, Moufida
AU - Bahmani, Baharak
AU - Usuelli, Vera
AU - Zhao, Jing
AU - Sabiu, Gianmarco
AU - Seelam, Andy Joe
AU - Naini, Said Movahedi
AU - Balasubramanian, Hari Baskar
AU - Park, Youngrong
AU - Li, Xiaofei
AU - Khalefa, Salma Ayman
AU - Kasinath, Vivek
AU - Williams, MacKenzie D.
AU - Rachid, Ousama
AU - Haik, Yousef
AU - Tsokos, George C.
AU - Wasserfall, Clive H.
AU - Atkinson, Mark A.
AU - Bromberg, Jonathan S.
AU - Tao, Wei
AU - Fiorina, Paolo
AU - Abdi, Reza
N1 - Publisher Copyright:
© 2023 Wiley-VCH GmbH.
PY - 2023/10/5
Y1 - 2023/10/5
N2 - 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.
AB - 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.
KW - drug delivery
KW - high endothelial venules
KW - nanomedicine
KW - targeted therapy
KW - type 1 diabetes
UR - https://www.scopus.com/pages/publications/85168287422
U2 - 10.1002/adma.202300812
DO - 10.1002/adma.202300812
M3 - Article
C2 - 37357903
AN - SCOPUS:85168287422
SN - 0935-9648
VL - 35
JO - Advanced Materials
JF - Advanced Materials
IS - 40
M1 - 2300812
ER -
