Doxorubicin (Dox) is one of the most commonly used and highly effective
antineoplastic agents, but the clinical application of this broad spectrum drug is largely hampered by its poor stability and serious toxicity to normal tissues. Hence, it is essential to improve the
therapeutic effect and decrease the systematic toxicity for the administration of
doxorubicin. In our study,
doxorubicin was incorporated into monomethoxy poly(
ethylene glycol)-poly(ε-
caprolactone) (
MPEG-PCL)
micelle by a self-assembly method. The cytotoxicity and cellular uptake efficiency of Dox-loaded
MPEG-PCL (Dox/
MPEG-PCL)
micelle against B16-F10 murine
melanoma cells was examined by the methylthiazoltetrazolium (MTT) test and flow cytometry. The antitumor activity of Dox/
MPEG-PCL was evaluated in C57BL/6 mice injected subcutaneously with B16-F10 cells. Toxicity was evaluated in
tumor-free mice. Meanwhile,
tumor proliferation, intratumoal angiogenesis and apoptotic cells were evaluated by
PCNA, CD31 staining and TUNEL assay, respectively. Encapsulation of
doxorubicin in
MPEG-PCL micelle improved the cytotoxicity of
doxorubicin and enhanced its cellular uptake on B16-F10 cell in vitro. Administration of Dox/
MPEG-PCL micelle resulted in significant inhibition (75% maximum inhibition relative to controls) in the growth of B16-F10
tumor xenografts and prolonged the survival of the treated mice (P<0.05). These anti-
tumor responses were associated with marked increase of
tumor apoptosis and notable reduction of cell proliferation and intratumoral microvessel density (P<0.05). The system toxicity also decreased in the Dox/
MPEG-PCL group compared with free
doxorubicin group. Our data indicate that the encapsulation of
doxorubicin in
MPEG-PCL micelle improved the anti-
tumor activity in vivo without conspicuous systemic toxic effects.