| First Author | Look M | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 4 | Pages | 1741-9 |
| PubMed ID | 23454752 | Mgi Jnum | J:197565 |
| Mgi Id | MGI:5493376 | Doi | 10.1172/JCI65907 |
| Citation | Look M, et al. (2013) Nanogel-based delivery of mycophenolic acid ameliorates systemic lupus erythematosus in mice. J Clin Invest 123(4):1741-9 |
| abstractText | The ability to selectively inactivate immune cells with immunosuppressants is a much sought-after modality for the treatment of systemic lupus erythematosus and autoimmunity in general. Here, we designed and tested a novel nanogel drug delivery vehicle for the immunosuppressant mycophenolic acid (MPA). Treatment with MPA-loaded nanogels increased the median survival time (MST) of lupus-prone NZB/W F1 mice by 3 months with prophylactic use (MST was 50 weeks versus 38 weeks without treatment), and by 2 months when administered after the development of severe renal damage (MST after proteinuria onset was 12.5 weeks versus 4 weeks without treatment). Equivalent and greater doses of MPA administered in buffer were not efficacious. Nanogels had enhanced biodistribution to organs and association with immune cells. CD4-targeted nanogels yielded similar therapeutic results compared with nontargeted formulations, with protection from glomerulonephritis and decreases in IFN-gamma-positive CD4 T cells. DCs that internalized nanogels helped mediate immunosuppression, as they had reduced production of inflammatory cytokines such as IFN-gamma and IL-12. Our results demonstrate efficacy of nanogel-based lupus therapy and implicate a mechanism by which immunosuppression is enhanced, in part, by the targeting of antigen-presenting cells. |
