Immunoliposome targeting to mesangial cells: a promising strategy for specific drug delivery to the kidney.
Mesangial cell-mediated nephropathies are a frequent cause of ESRD. Specific drug delivery to mesangial cells might be more effective and better tolerated than existing systemic treatments. Rat mesangial cells are characterized by Thy1.1 antigen expression. Therefore, OX7-coupled immunoliposomes (OX7-IL) were prepared by coupling liposomes with F(ab') fragments of OX7 mAb directed against Thy1.1 antigen. As the glomerular endothelium is fenestrated and no basement membrane separates glomerular capillaries from the mesangium, mesangial cells represent a particularly suitable target for drug delivery by OX7-IL. Therefore, the targeting efficacy of OX7-IL to mesangial cells was investigated. Specific targeting in vitro was obtained, and intravenous injection of OX-7-IL to rats showed a specific targeting of all mesangial cells in both kidneys. OX7-IL showed marked accumulation in the cytoplasm of rat mesangial cells, both in vitro and in vivo. This renal targeting was blocked when free OX7 F((ab')2) fragments were co-administered with OX7-IL. Rats that were given a single intravenous injection of low-dose doxorubicin encapsulated in OX7-IL showed extensive glomerular damage, whereas other parts of the kidney and other organs were spared. Free doxorubicin and the liposomal formulation of this agent had no effect. Thus, immunoliposomes are a very promising delivery system for the treatment of kidney diseases.
Tuffin
Gérald
G
Division of Nephrology, Inselspital, Bern, Switzerland. gerald.tuffin@dkf.unibe.ch
Waelti
Ernst
E
Huwyler
Jörg
J
Hammer
Caroline
C
Marti
Hans-Peter
HP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000938:Antigen-Presenting Cells; D001692:Biological Transport; D002460:Cell Line; D004317:Doxorubicin / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005434:Flow Cytometry; D005920:Glomerular Mesangium / Q000502:physiology*; D007668:Kidney / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D008081:Liposomes; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin