ROS-responsive thioether-based nanocarriers for efficient pro-oxidant cancer therapy

• Published in: Journal of industrial and engineering chemistry (Seoul, Korea) Vol. 75; pp. 238 - 245
• Main Authors: Kim, Yoon-Seok, Kim, Sumin, Kang, Han Chang, Shim, Min Suk
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 25-07-2019; 한국공업화학회
• Subjects: Cancer therapy; Nanoparticles; Piperlongumine; Pro-oxidant therapy; Thioether; 화학공학; Thioether; Nanoparticles; Piperlongumine; Cancer therapy; Pro-oxidant therapy
• ISSN: 1226-086X; 1876-794X
• DOI: 10.1016/j.jiec.2019.03.030

ROS-responsive thioether-bearing polymers (TEP) were synthesized and used as drug carriers for intracellular delivery of piperlongumine (PL) in cancer cells. The PL-loaded TEP nanoparticles exhibited ROS-triggered disassembly in cancer cells, leading to efficient cancer cell-specific apoptosis.
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A high level of intracellular reactive oxygen species (ROS) is one of the remarkable intrinsic features of cancer cells. Therefore, ROS-responsive drug carriers have received great attention for cancer-selective drug delivery. In this study, ROS-responsive thioether-bearing polymers (TEP) were synthesized for effective intracellular delivery of piperlongumine (PL) into cancer cells. PL is a pro-oxidant drug that induces cytotoxic oxidative stress in cancer cells. PL-loaded TEP nanoparticles (PL-TEP NPs) were successfully formulated by a nanoemulsion method. PL-TEP NPs showed ROS-sensitive disassembly, which leads to ROS-sensitive drug release. In addition, PL-TEP NPs showed higher cytotoxicity in human breast cancer cells (MCF-7) than in normal human dermal fibroblast cells (hDFB), demonstrating their cancer cell-specific pro-oxidant therapy. This study demonstrates that ROS-responsive TEP NPs are effective drug carriers for efficient intracellular delivery of hydrophobic drug, PL.