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Cell Rep. 2016 May 10;15(6):1202-13. doi: 10.1016/j.celrep.2016.04.007. Epub 2016 Apr 28.

Targeted Delivery of Immunomodulators to Lymph Nodes.

Author information

1
Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
2
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.
3
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
4
Department of Pathology, Clinical Laboratories Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
5
Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
6
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
7
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA. Electronic address: jianjunc@illinois.edu.
8
Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: rabdi@rics.bwh.harvard.edu.

Abstract

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.

PMID:
27134176
PMCID:
PMC4973867
DOI:
10.1016/j.celrep.2016.04.007
[Indexed for MEDLINE]
Free PMC Article

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