<jats:title>Abstract</jats:title> <jats:p>The pathogenesis of systemic lupus erythematosus is mediated by collaborations between CD4 T cells and B cells with autoantibody production. We propose that the use of biodegradable, nanoparticulate materials that are targeted against CD4 T cells and carry immunosuppressive drugs and proteins can be used to treat lupus. Biodegradable nanoparticles exhibit excellent therapeutic features such as biocompatibility, targeting potential, and controlled release rates of its encapsulated cargo. Here, we report results demonstrating the therapeutic efficacy of using nanoparticles to suppress lupus in NZB/W F1 mice, a lupus prone animal model. NZB/W F1 mice were administered weekly treatments of nanoparticle therapy, and disease progression and survival were monitored. Results show that nanoparticle therapy can delay disease progression and improve survival, using an immunosuppressive drug dosage in nanoparticles that is at least 16-fold less than the amount of immunosuppressive drug administered in buffer. These results suggest that nanoparticle immunotherapy can be used to effectively treat lupus at a lower dosage amount and frequency of dosage than conventional therapeutic regimens.</jats:p> <jats:p>This research is funded by the Wallace H. Coulter Foundation. ML is funded by a National Defense Science and Engineering Graduate (NDSEG) fellowship from the U.S. Department of Defense.</jats:p>