Cell Reports
(May 2016)
Targeted Delivery of Immunomodulators to Lymph Nodes
Jamil Azzi,
Qian Yin,
Mayuko Uehara,
Shunsuke Ohori,
Li Tang,
Kaimin Cai,
Takaharu Ichimura,
Martina McGrath,
Omar Maarouf,
Eirini Kefaloyianni,
Scott Loughhead,
Jarolim Petr,
Qidi Sun,
Mincheol Kwon,
Stefan Tullius,
Ulrich H. von Andrian,
Jianjun Cheng,
Reza Abdi
Affiliations
Jamil Azzi
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Qian Yin
Department of Materials Science and Engineering, University of Illinois at Urbana−Champaign, Urbana, IL 61820, USA
Mayuko Uehara
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Shunsuke Ohori
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Li Tang
Department of Materials Science and Engineering, University of Illinois at Urbana−Champaign, Urbana, IL 61820, USA
Kaimin Cai
Department of Materials Science and Engineering, University of Illinois at Urbana−Champaign, Urbana, IL 61820, USA
Takaharu Ichimura
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Martina McGrath
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Omar Maarouf
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Eirini Kefaloyianni
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Scott Loughhead
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
Jarolim Petr
Department of Pathology, Clinical Laboratories Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Qidi Sun
Department of Materials Science and Engineering, University of Illinois at Urbana−Champaign, Urbana, IL 61820, USA
Mincheol Kwon
Department of Materials Science and Engineering, University of Illinois at Urbana−Champaign, Urbana, IL 61820, USA
Stefan Tullius
Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Ulrich H. von Andrian
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
Jianjun Cheng
Department of Materials Science and Engineering, University of Illinois at Urbana−Champaign, Urbana, IL 61820, USA
Reza Abdi
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
DOI
https://doi.org/10.1016/j.celrep.2016.04.007
Journal volume & issue
Vol. 15,
no. 6
Abstract
Read online
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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