PEGylated Dendrimer-Doxorubicin Cojugates as pH-Sensitive Drug Delivery Systems: Synthesis and <I>In Vitro</I> Characterization

To achieve liver-specific delivery of antitumor drug doxorubicin (DOX), PEGylated dendrimer-DOX conjugates were designed and synthesized, whereas DOX was conjugated to dendrimers via hydrazone bonds and the dendrimers were functionalized with galactose moieties. The release rates of DOX from the conjugates at pH 5.0 were much faster than those at pH 7.4 due to the pH-sensitive cleavage of the hydrazone bonds. The conjugates were shown to effectively kill HepG2 cells in vitro. Compared to other conjugates, the PEGylated dendrimer-DOX one with multiple galactose moieties (Dendrimer-DOX-PEG-Gal) demonstrated HepG2 cells specificity, higher efficacy and good biosafety due to the lower IC50 value and higher cellular uptake confirmed by in vitro cytotoxicity assays, confocal laser scanning microscopy and flow cytometric studies. These results suggest that Dendrimer-DOX-PEG-Gal is an efficient and biocompatible candidate for the specific delivery of antitumor drug to HepG2 cells and could be used as liver cancer specific drug delivery system.