Amplification of oxidative stress: Via intracellular ROS production and antioxidant consumption by two natural drug-encapsulated nanoagents for efficient anticancer therapy

Cancer cells are commonly characterized by high cellular oxidative stress and thus have poor tolerance to oxidative insults. In this study, we developed a nano-formulation to elevate the level of reactive oxygen species (ROS) in cancer cells via promoting ROS production as well as weakening cellular anti-oxidizing systems. The nanoagent was fabricated by encapsulating two natural product molecules, cinnamaldehyde (CA) and diallyl trisulfide (DATS), in PLGA-PEG copolymer formulated nanoparticles. CA promotes ROS generation in cancer cells and DATS depletes cellular glutathione. CA and DATS exhibited a synergistic effect in amplifying the ROS levels in cancer cells and further in their combined killing of cancer cells. The in vivo experiments revealed that the CA and DATS-encapsulated nanoagent suppressed tumors more efficiently as compared with the single drug-loaded ones, and the tumor-targeted delivery further enhanced the therapeutic efficacy. This study suggests that the combined enhancement of oxidative stress by CA and DATS could be a promising strategy for cancer therapy.