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.
Highlights
Chemotherapy is one of the most common types of treatment for cancer, which can be used either alone or in combination with other therapies, such as surgery and radiation therapy [1]
Piperlongumine was supplied from Cayman Chemical (Ann Arbor, MI, USA). hDFB human dermal fibroblast cells and PC-3 human prostate cancer cells were obtained from ATCC (Manassas, VA, USA)
PL-CS–F NPs were synthesized by the ionic gelation cross-linking of chitosan and fucoidan
Summary
Chemotherapy is one of the most common types of treatment for cancer, which can be used either alone or in combination with other therapies, such as surgery and radiation therapy [1]. Many conventional anticancer drugs suffer some limitations, such as poor aqueous solubility, short blood circulation, and lack of cell-specificity [2,3]. Nanoparticle-based drug carriers have attracted great attention in cancer chemotherapy, because they can offer many benefits including an enhanced aqueous solubility of chemodrugs, prolonged blood circulation time, increased cellular uptake, and enhanced accumulation in tumors [4,5]. Natural polymers have been widely utilized for the preparation of nanoparticle-based drug carriers, because of their excellent biocompatibility [7]. A natural cationic polymer derived from chitin, has been intensively utilized as a safe drug carrier because of its biocompatible and biodegradable properties [8,9,10]. Previous studies have demonstrated that chitosan-based nanoparticles hold high potential for the safe and efficient delivery of anticancer drugs [8,11]
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