Overcoming multidrug resistance through co-delivery of ROS-generating nano-machinery in cancer therapeutics

The use of nanotechnology to overcome multidrug resistance (MDR) in cancer cells has been predominant. Herein, we report the conjugation of copper(II)-doxorubicin complexes on the surfaces of layered double hydroxide nanoparticles (LDHs) along with ascorbic acid intercalation in the gallery space to demonstrate synergistic effects to conquer MDR. The pH-sensitive release of doxorubicin (Dox) and the sustained release of ascorbic acid (AA) generate high amounts of hydrogen peroxide intracellularly that concomitantly results in conversion to cytotoxic free radicals through a copper(II)-catalyzed Fenton-like reaction. Therefore, the combination of the chemotherapeutic agent (Dox) and free radical attack can devastate the MDR for effective cancer treatment through the co-delivery system.