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.