In vivo studies on mouse erythrocytes linked to transferrin.
Transferrin (Tf), a plasma protein with numerous, highly specific receptors in proliferating and differentiating cells was already discussed as a targeting ligand for drugs and liposomes in previous studies. In this paper, we deal with erythrocytes linked to Tf as possible physiological targeting carrier systems for delivering anticancer drugs. For that purpose we have used glutaraldehyde (0.1%) as a coupling agent between Tf and erythrocytes. The highest amount of Tf linked to erythrocytes turned out to be 0.76 +/- 0.13 microg Tf/10(6) cells, while reaching 65% of cell recovery. After 13 days, the Tf-erythrocytes hemolysis reached 50%, with transferrin still coupled to erythrocytes. The in vivo kinetic behaviour of intravenously injected 51Cr-Tf-erythrocytes showed a reduced half-life to hours as compared to days of controls. However, a considerable percentage of Tf-erythrocytes (close to 20%) remained circulating for a relatively long period (around 2 days), which made possible the specific targeting by these carrier systems. In vivo biodistribution studies indicated that 51Cr-Tf-erythrocytes rapidly accumulated in the different studied organs (liver, spleen, lungs, kidneys, femur-tibia, and heart), suggesting a selective removal of Tf-erythrocytes by the cells of the mononuclear phagocytic system present mainly in liver and spleen. On the other hand, Tf-erythrocytes showed a poor targeting of heart tissue, therefore a reduced cardiac toxicity should be expected after administration of erythrocyte-encapsulated drugs. The presence of Tf-erythrocytes in femur-tibia and spleen could be related to the Tf-specific binding to the hematopoietic cells containing Tf receptors. The final results of this study encourage additional research on Tf-erythrocyte to investigate the relationship between transferrin-mediated targeting by carrier erythrocytes and uptake of different erythrocyte-encapsulated drugs. Consequently, the current study showed possible use of these carriers as a potential therapeutic tool for drug targeting in animal models with alterations affecting mononuclear phagocytic system or carcinomas of various origins whose cells show elevated number of Tf receptors.
Pérez
M Teresa
MT
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Campus Universitario, E-28871, Alcalá de Henares, Madrid, Spain.
García-Pérez
Ana Isabel
AI
Pinilla
Montserrat
M
Sancho
Pilar
P
D000818:Animals; D004912:Erythrocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D014168:Transferrin / Q000378:metabolism*
D014168:Transferrin