Efficient and selective cancer therapy using pro-oxidant drug-loaded reactive oxygen species (ROS)-responsive polypeptide micelles

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High levels of intracellular reactive oxygen species (ROS) in cancer cells have emerged as a cancer-specific stimulus that can be utilized for anticancer therapy. Therefore, ROS-responsive drug carriers have attracted considerable attention as cancer-specific drug delivery systems. In this study, an ROS-responsive poly(ethylene glycol)-poly(methionine) [PEG-P(Met)] was synthesized to achieve safe and effective delivery of piperlongumine (PL), a pro-oxidant drug, into cancer cells. Nanoscale core-shell micelles encapsulating hydrophobic PL into a P(Met) core were prepared by self-assembling. The increased ROS levels in cancer cells triggered a hydrophobic-to-hydrophilic transition of the polypeptide, which led to the ROS-responsive disassembly of the micelles and consequently efficient PL release into cancer cells. Compared to free PL, PL-loaded PEG-P(Met) [(PL-PEG-P(Met)] micelles exhibited enhanced apoptosis in MCF-7 human breast cancer cells owing to the efficient intracellular delivery of PL. Notably, the PL-PEG-P(Met) micelles exhibited cancer-specific cytotoxicity in MCF-7 human breast cancer cells owing to a considerable increase in intracellular ROS level in the cells. These results demonstrate that the ROS-responsive PEG-P(Met)-based micelles are safe and effective drug carriers for intracellular delivery of PL, which can provide cancer-selective pro-oxidant therapy. (c) 2020 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE INC
Issue Date
2021-03
Language
English
Article Type
Article
Citation

JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY, v.95, pp.101 - 108

ISSN
1226-086X
DOI
10.1016/j.jiec.2020.12.009
URI
http://hdl.handle.net/10203/281464
Appears in Collection
CBE-Journal Papers(저널논문)
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