Scindia Y et al. (2008) Anti-8 integrin immunoliposomes in glomeruli of lupus-susceptible mice: a novel system for delivery of therapeutic agents to the renal glomerulus in systemic lupus erythematosus. Arthritis Rheum 58: 3884–3891

Cell proliferation, secretion of inflammatory cytokines, and production of extracellular matrix by glomerular mesangial cells are implicated in the pathogenesis of lupus glomerulonephritis. Targeting mesangial cells might, therefore, provide an effective treatment strategy for patients with systemic lupus erythematosus. However, identification of a surface marker unique to these cells has so far proved elusive, as has a mode for targeted drug delivery. Immunoliposomes—conjugates of liposomes and antibodies—have now been used to target the surface marker α8 integrin.

Normal and nephritic mice express α8 integrin in their glomeruli. Optimally designed anti-α8 integrin immunoliposomes loaded with a fluorescent tracking dye (DiI) were injected into the tail vein of (NZM × NOD)F1 mice, a model of spontaneous systemic lupus erythematosus. The anti-α8 integrin immunoliposomes, but not control rabbit IgG immunoliposomes, were detected specifically in glomerular mesangium and mesangial cells in 2-month-old mice (which show no pathologic changes at this age) and in 6-month-old mice (which show signs of mesangial expansion, indicative of acute proliferative glomerulonephritis); the formation of glomerular IgG immune complex deposits in 6-month-old mice did not interfere with this specific targeting.

Trafficking of the DiI-loaded anti-α8 integrin immunoliposomes into other tissues was infrequent and nonspecific and, as human cells also express α8 integrin, targeted delivery by this mode has the potential to provide selective treatment for glomerular diseases in humans.