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Nanotargeted Delivery of Immune Therapeutics in Type 1 Diabetes.
Jung, Sungwook; 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.
Afiliação
  • Jung S; Transplantation Research Center and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Ben Nasr M; Division of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Bahmani B; International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Università di Milano, 20157, Milan, Italy.
  • Usuelli V; Transplantation Research Center and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Zhao J; International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Università di Milano, 20157, Milan, Italy.
  • Sabiu G; Transplantation Research Center and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Seelam AJ; Transplantation Research Center and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Naini SM; Transplantation Research Center and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Balasubramanian HB; Transplantation Research Center and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Park Y; International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Università di Milano, 20157, Milan, Italy.
  • Li X; Transplantation Research Center and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Khalefa SA; Transplantation Research Center and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Kasinath V; International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Università di Milano, 20157, Milan, Italy.
  • Williams MD; Transplantation Research Center and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Rachid O; Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, Diabetes Institute, University of Florida, Gainesville, FL, 32610, USA.
  • Haik Y; Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, 2713, Doha, Qatar.
  • Tsokos GC; Department of Mechanical and Nuclear Engineering, University of Sharjah, 27272, Sharjah, UAE.
  • Wasserfall CH; Division of Rheumatology and Clinical Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA.
  • Atkinson MA; Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, Diabetes Institute, University of Florida, Gainesville, FL, 32610, USA.
  • Bromberg JS; Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, Diabetes Institute, University of Florida, Gainesville, FL, 32610, USA.
  • Tao W; Department of Pediatrics, University of Florida, Gainesville, FL, 32610, USA.
  • Fiorina P; Departments of Surgery and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
  • Abdi R; Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Adv Mater ; 35(40): e2300812, 2023 Oct.
Article em En | MEDLINE | ID: mdl-37357903
ABSTRACT
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Tipo 1 Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Tipo 1 Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article