Precise ratiometric co-loading, co-delivery and intracellular co-release of paclitaxel and curcumin by aid of their conjugation to the same gold nanorods to exert synergistic effects on MCF-7/ADR cells

It is necessary for effective combinational effects that multiple chemotherapeutic agents enter and act on the same tumor cells simultaneously at a suitable ratio. Due to their individual physicochemical or biopharmaceutical properties, they cannot reach the same cells at its predetermined ratio after co-administration. Herein, we report a novel system with precise ratiometric co-loading, co-delivery and intracellular co-release of paclitaxel (PTX) and curcumin (CUR), to investigate their synergistic effects. We prepared the system by conjugating PTX and CUR at different ratios onto the same gold nanorods (GNRs). We demonstrated that PTX and CUR could be precisely ratiometric co-loaded to form dual-drug conjugated biotin-PEG modified GNRs (abbreviated as PTX/ [email protected] ), which could co-deliver dual drugs into tumor cells with a predetermined ratio and co-release them intracellularly. The PTX/ [email protected] with the mass ratio of PTX and CUR at 1:1 exhibited the best synergistic effect on multidrug resistant MCF-7/ADR cells while the free PTX and CUR mixture with the mass ratio of at 1:0.75 displayed the strongest synergism. Cytotoxicity studies showed that PTX/ [email protected] are superior to free drug mixture. Furthermore, PTX/ [email protected] could remarkably induce apoptosis of MCF-7/ADR cells under near-infrared irradiation. Moreover, we found that PTX/ [email protected] significantly inhibited P-glycoprotein (P-gp) expression in MCF-7/ADR cells.