期刊
JOURNAL OF DRUG TARGETING
卷 8, 期 2, 页码 67-77出版社
HARWOOD ACAD PUBL GMBH
DOI: 10.3109/10611860008996853
关键词
colchicine; Fab; HL 60 cells; IgG; pharmacokinetics; protein cationization; transfer permeability
Antibodies are poorly transported across cell membranes and biological barriers in vivo. Cationization of antibody molecules by the derivatization of surface carboxyl groups generating primary amino groups could represent a strategy for intracellular antibody delivery. Before cationization of polyclonal colchicine-specific IgG and Fab, using hexamethylenediamine the isoelectric point (pI) of native IgG and Fab (nIgG and nFab) was in the range of 5.9-9.0 and 8.7-9.3, respectively, The pi of cationized IgG and Fab (cIgG and cFab) were both higher at 8.7-10.3 and 9.5-11, respectively. The affinity and specificity of both IgG and Fab were not modified by cationization, When HL 60 cells were incubated with the native or cationized I-125-BSA, -IgG and -Fab, the maximal cellular uptake of cIgG and cFab was 3.2 and 2.4 times higher than that of nIgG and nFab at an extracellular concentration of 500 ng/ml, Results also indicated that the uptake was dose- and temperature-dependent suggesting absorptive-mediated endocytosis of cationized antibodies by HL 60 cells, Confocal microscopy analysis indicated that the cationized antibodies were present in the plasma membranes and cytoplasm of HL 60 cells, Finally, a study with bovine arterial endothelial monolayer cells showed that the transport of cIgG and cFab through the monolayer cells was 3.3- and 4.3-fold higher for I-125-cIgG and I-125-cFab than those of the corresponding native forms.
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