Heparin drug conjugates are currently investigated as excellent candidates for
drug delivery vehicles. In this study, we report the preparation and characterization of dendronized
heparin-doxorubicin (
heparin-DOX) conjugate as pH-sensitive
drug delivery vehicle by combination of the features of
dendrimer and
heparin. Dynamic light scattering (DLS) and transmission electron microscope (TEM) studies demonstrated the dendronized
heparin-DOX conjugate self-assembled into compact nanoparticles with negatively charged surface. The nanoparticles with 9.0 wt% (weight percent) of
doxorubicin (DOX) showed pH-sensitive property due to the faster drug release rate at pH 5.0 and slow release rate at pH 7.4 aqueous. The nanoparticles were shown to effectively kill
cancer cells in vitro. Notablely, the nanoparticles resulted in strong antitumor activity, high
antiangiogenesis effects and induced apoptosis on the 4T1
breast tumor model due to the evidences from mice weight shifts,
tumor weights,
tumor growth curves, immunohistochemical assessment and histological analysis. It's also noteworthy that dendronized
heparin and its nanoparticle with
drug demonstrated no significant toxicity to healthy organs of both
tumor-bearing and healthy mice, which was confirmed by histological analysis compared with free
drug DOX. The dendronized
heparin-DOX conjugate based nanopatilce with high antitumor activity and low side effects may be therefore a potential nanoscale
drug delivery vehicle for
breast cancer therapy.