Targeting anti-transferrin receptor antibody (OX26) and OX26-conjugated liposomes to brain capillary endothelial cells using in situ perfusion.
Brain capillary endothelial cells (BCECs) express transferrin receptors. The uptake of a potential drug vector (OX26, or anti-transferrin receptor antibody IgG2a) conjugated to polyethyleneglycol-coated liposomes by BCECs was studied using in situ perfusion in 18-day-old rats in which the uptake of OX26 is almost twice as high as in the adult rat. Using radio-labeling, the uptake of OX26 by BCECs after 15-minute perfusion was approximately 16 times higher than that of nonimmune IgG2a (Ni-IgG2a). OX26 and OX26-conjugated liposomes selectively distributed to BCECs, leaving choroid plexus epithelium, neurons, and glia unlabeled. Ni-IgG2a and unconjugated liposomes did not reveal any labeling of BCECs. The labeling of BCECs by OX26 was profoundly higher than that of transferrin. Perfusion with albumin for 15 minutes did not reveal any labeling of neurons or glia, thus confirming the integrity of the blood-brain barrier. The failure to label neurons and glia shows that OX26 and OX26-conjugated liposomes did not pass through BCECs. The expression of transferrin receptors by endothelial cells selective to the brain qualifies OX26 as a candidate for blood-to-endothelium transport. A specifically designed formulation of liposomes may allow for their degradation within BCECs, leading to subsequent transport of liposomal cargo further into the brain.
Gosk
Sara
S
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Vermehren
Charlotte
C
Storm
Gert
G
Moos
Torben
T
D000418:Albumins / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D008081:Liposomes / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D009532:Nickel; D010477:Perfusion / Q000379:methods*; D011092:Polyethylene Glycols; D021381:Protein Transport; D051381:Rats; D011990:Receptors, Transferrin / Q000032:analysis / Q000276:immunology* / Q000378:metabolism
D000418:Albumins; D007074:Immunoglobulin G; D008081:Liposomes; D011990:Receptors, Transferrin; D011092:Polyethylene Glycols; D009532:Nickel