Reversion of Multidrug Resistance Using Self-Organized Nanoparticles Holding Both Doxorubicin and Targeting Moiety
Doxorubicin and galactose were chemically conjugated to dextran by the carboxypropyl spacers and the conjugate was formulated into nanoparticle with free doxorubicin. The content of doxorubicin was as high as 17.2% in the nanoscale drug delivery systems (nano-DDSs) and the nanoparticle size was less than 190 nm. In an in vitro cytotoxicity experiment, the nano-DDSs had higher cytotoxicity than free DOX against the drug resistant HepG2 cells. In a human tumor xenograft nude mouse model, the nano-DDSs generated higher therapeutic effect than free doxorubicin. These promising data show a better anti-tumor efficacy on drug resistant HepG2 cells of nano-DDSs versus free doxorubicin, and warrant further studies in both animals and humans.
Keywords: Targeting nanoparticles, Hepatocellular carcinoma, Drug resistance, Cancer therapy, Drug delivery
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