The
therapeutic effect of
methotrexate (MTX)-conjugated
Pluronic-based polymeric mixed
micelles (
F127/P105-MTX) on the
folate receptor-overexpressing
tumors treatment was investigated in this study. Due to its high structural similarity to
folic acid and the high expression of
folate receptor in most solid
tumors, MTX serves as not only a
cytotoxic agent but also a homing
ligand. Cellular uptake and the endocytic mechanism studies of MTX-conjugated mixed
micelles were performed in
folate receptor-rich KBv and
folate receptor-deficient A-549
cancer cells. Additionally, the efficacy and safety studies of
F127/P105-MTX in KBv
tumor-bearing mice were evaluated. Results indicate that
F127/P105-MTX significantly enhanced the cellular uptake in KBv cells as compared to that of conventional non-MTX-conjugated mixed
micelles. Moreover, the results showed that
F127/P105-MTX can be internalized by both caveolae- and
clathrin-mediated endocytosis in energy-dependent and
folate receptor-dependent manners. The in vitro and in vivo antitumor efficacies of
F127/P105-MTX were significantly enhanced in comparison with MTX-entrapped mixed
micelles. Furthermore, no acute toxicities to hematological system and major organs have been observed after
intravenous administration during the regimen. Therefore, our results suggest that
F127/P105-MTX could be an effective and safe
nano-drug delivery system for
cancer therapy, especially for the
folate receptor-rich
cancer treatment.