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

• Published in: Nanoscale advances 2020-09, Vol.2 (9), p.3872-3881
• Main Authors: Liu, Yihuan, Liu, Haibin, Wang, Li, Wang, Yingjie, Zhang, Chengcheng, Wang, Changping, Yan, Yang, Fan, Jingpin, Xu, Guanghui, Zhang, Qiang
• Format: Article
• Language: English
• ISSN: 2516-0230
• DOI: 10.1039/d0na00301h

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. A nanoagent delivering two natural product molecules to promote ROS generation as well as to consume intracellular antioxidant is developed for oxidative stress-associated anticancer therapy.