Transferrin receptor targeting

Kobayashi T, Ishida T, Okada Y, Ise S, Harashima H, Kiwada H. Effect of transferrin receptor-targeted liposomal doxorubicin in p-glycoprotein-mediated drug resistant tumor cells. Tnt J Pharm 2007 329 94—102. 

Chiu S, Liu S, Perrotti D et al (2006) Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes. J Control Release 112 199-207... 

Raso, V., and Basala, M. (1985) Study of the transferrin receptor using a cytotoxic human transferrin-ricin A chain conjugate. In Receptor-Mediated Targeting of Drugs, (G. Gregoriadis, ed.), Vol. 2, p. 73. Plenum, New York. 

However, the greatest changes in the biodistribution of HPMA copolymers were achieved, as expected, by the attachment of targeting moieties. A number of targeting moieties were used (N-acylated) galactosamine [23,39,40, 43, 113,191, 260-265,270-272], (6-O-bound) galactose [162,272], (N-acylated) fucosylamine [39,40,264], anti-Thy 1.2 antibodies and anti Iak antibodies [23, 24, 41, 273-275], B 72.3 antibodies [276], transferrin and anti-transferrin receptor (B3/25) antibodies [277], anti-CD3 antibodies [344] melanocyte stimulating hormone [37], and secretin [278,279]. 

Penichet ML, et al. An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting initial applications in anti-HIV antisense drug delivery to the brain. J Immunol 1999 163(8) 4421—4426. 

Qian, Z.M., et al. 2002. Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol Rev 54 561. 

Gosk, S., et al. 2004. Targeting anti-transferrin receptor antibody (0X26) and OX26-conjugated liposomes to brain capillary endothelial cells using in situ perfusion. J Cereb Blood Flow Metab 24 1193. 

West AE, Neve RL, Buckley KM. Identification of a somatodendritic targeting signal in the cytoplasmic domain of the transferrin receptor. J Neurosci 1997 17 6038-6047. 

In the context of dmg delivery, certain cell surface receptor and ion-channel families are particularly appealing as dmg delivery targets. Well-characterized examples include the lectin-like receptor gene family as receptors for glycosylated molecules, as well as vitamin- and trace element-uptake systems such as the transferrin-receptor. 

Schnyder et al. explored the targetability of biotinylated immunoliposomes to skeletal muscle cell line in vitro [185], 0X26 mAb binds to transferrin receptor and is covalently attached to streptavidin by introducing thiol groups using 2-iminothio-lane (Traut s reagent). Immunoliposomes consisted of DSPC (5.2pmol), cholesterol... 

As noted above, iron-loaded serum transferrin has the role of transporting Fe(III) to cells requiring it. Once it reaches a target cell, it binds to the transferrin receptor (TfR) on the cell outer surface. TfR is a disulfide-linked dimer that binds two transferrin molecules. At neutral pH, apo transferrin does not bind to the transferrin receptor. Once formed, the transferrin receptor complex becomes detached from the cell membrane and enters the cell enclosed in a clathrin-coated vesicle. Uncoating of the vesicle generates an endosome in which the pH is lowered to 5.5, promoting release of iron. At this pH, the transferrin remains bound to its receptor, and... 

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