TY - JOUR
T1 - Targeted Delivery of Immunomodulators to Lymph Nodes
AU - Azzi, Jamil
AU - Yin, Qian
AU - Uehara, Mayuko
AU - Ohori, Shunsuke
AU - Tang, Li
AU - Cai, Kaimin
AU - Ichimura, Takaharu
AU - McGrath, Martina
AU - Maarouf, Omar
AU - Kefaloyianni, Eirini
AU - Loughhead, Scott
AU - Petr, Jarolim
AU - Sun, Qidi
AU - Kwon, Mincheol
AU - Tullius, Stefan
AU - von Andrian, Ulrich H.
AU - Cheng, Jianjun
AU - Abdi, Reza
N1 - Funding Information:
This work was supported by an American Heart Association grant (to J.A.), the National Institute of Allergy and Infectious Diseases of the NIH under Award RO1AI091930 (to R.A.), and the NIH Director’s New Innovator Award 1DP2OD007246 (to J.C.). The synthesis of the polylactide-drug conjugates and nanoconjugates was partially supported by NSF-CHE-1308485. This research was also supported in part by a gift from Mr. Matthew S. Forelli. U.H.v.A. was supported by funds from the HMS Center for Immune Imaging and the Ragon Institute and by NIH grants AI112521, AI111595, and AR068383. Q.Y. was funded at the University of Illinois at Urbana−Champaign by NIH National Cancer Institute Alliance for Nanotechnology in Cancer (Midwest Cancer Nanotechnology Training Center) (R25 CA154015A). The synthesis of the polylactide-drug conjugates and nanoconjugates was partially supported by NSF-CHE-1308485.
Publisher Copyright:
© 2016 The Authors.
PY - 2016/5/10
Y1 - 2016/5/10
N2 - Active-targeted delivery to lymph nodes represents a major advance toward more effective treatment of immune-mediated disease. The MECA79 antibody recognizes peripheral node addressin molecules expressed by high endothelial venules of lymph nodes. By mimicking lymphocyte trafficking to the lymph nodes, we have engineered MECA79-coated microparticles containing an immunosuppressive medication, tacrolimus. Following intravenous administration, MECA79-bearing particles showed marked accumulation in the draining lymph nodes of transplanted animals. Using an allograft heart transplant model, we show that targeted lymph node delivery of microparticles containing tacrolimus can prolong heart allograft survival with negligible changes in tacrolimus serum level. Using MECA79 conjugation, we have demonstrated targeted delivery of tacrolimus to the lymph nodes following systemic administration, with the capacity for immune modulation in vivo.
AB - Active-targeted delivery to lymph nodes represents a major advance toward more effective treatment of immune-mediated disease. The MECA79 antibody recognizes peripheral node addressin molecules expressed by high endothelial venules of lymph nodes. By mimicking lymphocyte trafficking to the lymph nodes, we have engineered MECA79-coated microparticles containing an immunosuppressive medication, tacrolimus. Following intravenous administration, MECA79-bearing particles showed marked accumulation in the draining lymph nodes of transplanted animals. Using an allograft heart transplant model, we show that targeted lymph node delivery of microparticles containing tacrolimus can prolong heart allograft survival with negligible changes in tacrolimus serum level. Using MECA79 conjugation, we have demonstrated targeted delivery of tacrolimus to the lymph nodes following systemic administration, with the capacity for immune modulation in vivo.
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U2 - 10.1016/j.celrep.2016.04.007
DO - 10.1016/j.celrep.2016.04.007
M3 - Article
C2 - 27134176
AN - SCOPUS:84964595279
SN - 2211-1247
VL - 15
SP - 1202
EP - 1213
JO - Cell Reports
JF - Cell Reports
IS - 6
ER -