Synthesis and Reversal Efficacy of Magnetic Nanoparticles Coloaded with Daunorubicin and 5-Bromotetrandrin

Abstract 4945

Owing to serious side effects and multidrug resistance (MDR), systematic chemotherapy is limited in cancer treatment. On the one hand, most of side effects are result from non-selective for target cells of antitumor drugs. On the other hand, the main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). Design and exploitation of novel clinical chemotherapy formulation with dual functional properties of targeted therapy and reversal of drug resistance is a promising approach in tumor therapy. Nanoparticles drug delivery system has been shown to improve cancer therapy by increased drug delivery to target sites because of the enhanced permeability and retention effect (EPR). In the present studies, we developed a new formulation, which magnetic nanoparticles (MNPs) coloaded with daunorubicin (DNR) and 5-bromotetrandrin (Br Tet), an anticancer drug and a MDR reversal agent, and studied the in vitro antitumor efficacy. The drug encapsulation efficiency of DNR and Br Tet (alone or in combination) in MNPs was 62–83%. The release of DNR and Br Tet from nanoparticles was sustained. The DNR and Br Tet loaded MNPs (DNR-Br Tet-MNPs) are provided with good magnetic responsibility. The drugs in combination incorporated in MNPs displayed well synergistic cytotoxicity in the MDR leukemia K562/A02 cells. Fluorescence intensity of intracellular DNR detection demonstrated that DNR-Br Tet-MNPs could be endocytosed by K562/A02 cells and sustained releasing DNR intracellular. The results of RT-PCR and western blot demonstrated that the expressions of MDR1 mRNA and G-pg of K562/A02 cells are decreased by treated with DNR-Br Tet-MNPs after 48 h. It was concluded that the antitumor efficacy of DNR-Br Tet-MNPs was due to the inhibition of Br Tet to P-gp and reducing the efflux of DNR. Our DNR-Br Tet-MNPs could be of high clinical value in the target treatment of many resistant tumors, such as haematologic malignancies.