Co-encapsulated DOX(doxorubicin) and CUR(curcumin) in PBCA-NPs(polybutylcyanoacrylate nanoparticles) were prepared with emulsion polymerization in an attempt to show the improved growth inhibition efficacy in a resistant cell culture line. The mean particle size and the zeta potential of DOX-CUR-PBCA-NPs were 133 ± 5.34nm in diameter and +32.23 ± 4.56 mV, respectively. The entrapment efficiencies of DOX and CUR were 49.98 ± 3.32% and 94.52 ± 3.14% respectively. Anticancer activities and reversal efficacies of the formulations and various combination approaches were assessed using MTT assay and Western Blotting. The results showed that the dualagent loaded PBCA-NPs system had the similar cytotoxicity to co-administration of two single-agent loaded PBCANPs (DOX-PBCA-NPs + CUR-PBCA-NPs), which was slightly higher than that of the free drug combination (DOXCUR) and one free drug / another agent loaded PBCA-NPs combination (DOX+CUR-PBCA-NPs or CUR+DOXPBCA- NPs). The simultaneous administration of DOX and CUR could achieve the highest efficacy in terms of reversing multidrug-resistantance(MDR), and down-regulating P-gp in MCF-7/ADR cell lines. MDR reversal can be enhanced by treated combination of encapsulated cytotoxic drugs and reversal agents. Co-encapsulation of anticancer drug DOX and reversal agent CUR can be more effective in reversing multi-drug resistance than the other formulations and might cause lower normal tissue drug toxicity and fewer drug-drug interactions