Targeted Delivery of Immunomodulators to Lymph Nodes

被引：86

作者：

Azzi, Jamil ^{[1
]}

Yin, Qian ^{[5
]}

Uehara, Mayuko ^{[1
]}

Ohori, Shunsuke ^{[1
]}

Tang, Li ^{[5
]}

Cai, Kaimin ^{[5
]}

Ichimura, Takaharu ^{[1
]}

McGrath, Martina ^{[1
]}

Maarouf, Omar ^{[1
]}

Kefaloyianni, Eirini ^{[1
]}

Loughhead, Scott ^{[4
]}

Petr, Jarolim ^{[6
]}

Sun, Qidi ^{[5
]}

Kwon, Mincheol ^{[5
]}

Tullius, Stefan ^{[2
,3
]}

von Andrian, Ulrich H. ^{[4
,7
]}

Cheng, Jianjun ^{[5
]}

Abdi, Reza ^{[1
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr,Sch Med, Boston, MA 02115 USA

[2] Harvard Univ, Brigham & Womens Hosp, Div Transplant Surg, Sch Med, Boston, MA 02115 USA

[3] Harvard Univ, Brigham & Womens Hosp, Transplant Surg Res Lab, Sch Med, Boston, MA 02115 USA

[4] Harvard Univ, Dept Microbiol & Immunobiol, Sch Med, Boston, MA 02115 USA

[5] Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61820 USA

[6] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Div Clin Labs,Sch Med, Boston, MA 02115 USA

[7] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

来源：

CELL REPORTS | 2016年 / 15卷 / 06期

基金：

美国国家科学基金会;

关键词：

NONOBESE DIABETIC MICE; MEMORY T-CELLS; KIDNEY-TRANSPLANTATION; DRUG-DELIVERY; VASCULAR ADDRESSIN; ALLOGRAFT SURVIVAL; ADHESION PATHWAYS; IN-VIVO; NEPHROTOXICITY; CYCLOSPORINE;

D O I：

10.1016/j.celrep.2016.04.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1202 / 1213

页数：12

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