Selective Anticancer Therapy Using Pro-Oxidant Drug-Loaded Chitosan–Fucoidan Nanoparticles

Abstract

Pro-oxidant therapy exploiting pro-oxidant drugs that can trigger cytotoxic oxidative stress in cancer cells has emerged as an innovative strategy for cancer-specific therapy. Piperlongumine (PL) has gained great interest as a novel pro-oxidant agent, because it has an ability to trigger cancer-specific apoptosis through the increase of oxidative stress in cancer cells. However, the use of PL is limited in the clinic because of its hydrophobic nature. In this study, chitosan- and fucoidan-based nanoparticles were prepared for the effective intracellular delivery of PL into cancer cells. Chitosan and fucoidan formed nanoparticles by ionic gelation. The chitosan- and fucoidan-based nanoparticles (CS−F NPs) effectively encapsulated PL, and increased its water solubility and bioavailability. CS−F NPs showed very low cytotoxicity in human prostate cancer cells, demonstrating its high potential for in vivo applications. The PL-loaded chitosan−fucoidan nanoparticles (PL-CS−F NPs) efficiently killed human prostate cancer cells via PL-induced intracellular reactive oxygen species (ROS) generation. This study demonstrates that CS−F NPs are promising natural polymer-based drug carriers for safe and effective PL delivery.

Keywords

• chitosan
• fucoidan
• nanoparticles
• piperlongumine
• pro-oxidant cancer therapy