期刊
JOURNAL OF CONTROLLED RELEASE
卷 126, 期 1, 页码 44-49出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2007.11.001
关键词
active targeting; immunonanocapsules; OX26 MAb; transferrin receptor; brain
The present study shows the potential of novel nanovectors for the delivery of lipophilic radionuclides and therapeutic molecules to the brain. Lipid nanocapsules(LNC) inhibiting the P-gp pump efflux, were conjugated to OX26 monoclonal antibodies (OX26 MAb) and Fab' fragments. The OX26 MAb is directed against the transferrin receptor (TfR) highly expressed on the cerebral endothelium. The specific association of immunonanocapsules to rat brain capillary endothelial cells was demonstrated. Biodistribution of immunonanocapsules, labeled with a Re-188 lipophilic complex, was determined in healthy rats. At 24 h post-injection, the brain concentrations of Fab'-immunonanocapsules and OX26-immunonanocapsules were, respectively, 1.5 and 2-fold higher than non-targeted nanocapsules. In addition, Fab' fragments helped prolong the vascular residence time of the nanovectors but their affinity to TfR was lower than whole antibodies. The ability of immunonanocapsules to specifically target cerebral tissues in addition to the promising features of LNC is of importance to the field of nanomedicine. (C) 2007 Elsevier B.V. All rights reserved.
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