Redox nanoparticles inhibit curcumin oxidative degradation and enhance its therapeutic effect on prostate cancer

摘要

Curcumin is a phytochemical with diverse molecular targets and is well known for its anti-tumor potential. However, it has limited application in cancer therapy because curcumin undergoes rapid oxidative degradation at physiological conditions resulting in poor stability and bio-availability. In this study, we were able to suppress curcumin's oxidative degradation by encapsulating it in a nanoparticle that also acts as a radical scavenger. We prepared curcumin-loaded pH-sensitive redox nanoparticles (RNPN) by self-assembling amphiphilic block copolymers conjugated with reactive oxygen species (ROS) scavenging nitroxide radicals to ensure the delivery of minimally degraded curcumin to target regions. In vitro analysis confirmed that the entrapment of both curcumin and nitroxide radicals in the hydrophobic core of RNPN suppressed curcumin degradation in conditions mimicking the physiological environment. Evaluation of apoptosis-related molecules in the cells, such as ceramides, caspases, apoptosis-inducing factor, and acid ceramidase revealed that curcumin loaded RNPN induced strong apoptosis compared to free curcumin. Lastly, intravenous injection of curcumin loaded RNPN suppressed tumor growth in vivo, which is due to the increased bio-availability and significant ROS scavenging at tumor sites. These results demonstrated that RNPN is a promising drug carrier with unique ROS-scavenging abilities, and it is able to overcome the crucial hurdle of curcumin's limitations to enhance its therapeutic potential. (C) 2015 Elsevier B.V. All rights reserved.