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

• Published in: International journal of molecular sciences Vol. 20; no. 13; p. 3220
• Main Authors: Choi, Dae Gun, Venkatesan, Jayachandran, Shim, Min Suk
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-06-2019; MDPI
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Apoptosis; Cancer; Cancer therapies; Cell Death - drug effects; Cell Line; Cell Line, Tumor; Chemotherapy; Chitosan; Chitosan - analogs & derivatives; Cytotoxicity; Dioxolanes - administration & dosage; Dioxolanes - pharmacology; Dismantling; Drug carriers; Drug delivery; Drug dosages; Endocytosis; Fourier transforms; Fucoidan; Humans; Hydrophobicity; Internalization; Intracellular; Nanoparticles; Nanoparticles - adverse effects; Nanoparticles - chemistry; Oxidants; Oxidants - administration & dosage; Oxidants - pharmacology; Oxidative stress; Oxidizing agents; piperlongumine; Polymers; Polysaccharides - chemistry; pro-oxidant cancer therapy; Spectrum analysis; chitosan; piperlongumine; pro-oxidant cancer therapy; nanoparticles; fucoidan
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20133220

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.