한빛사논문
가톨릭대학교 의과대학
Giuk Leea,1, Chan Woo Kimb,c,1, Jeong Ryul Choia,1, Kyung Hyun Mind, Hong Jae Leee, Kyu Hwan Kwackf, Hyeon-Woo Leef, Jae-Hyung Leeg, Seo Young Jeonga, Kiyuk Changb,c,*, Sang Cheon Leee,*
aDepartment of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
bDivision of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
cCatholic Research Institute for Intractable Cardiovascular Disease, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
dDepartment of Pharmacy, School of Pharmacy, Jeonbuk National University, Jeonbuk 54896, Republic of Korea
eDepartment of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea
fDepartment of Pharmacology, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea
gDepartment of Oral Microbiology, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea
1These authors contributed equally to this work.
*Corresponding authors.
Abstract
We report copper(II) arsenite (CuAS)-integrated polymer micelles (CuAS-PMs) as a new class of Fenton-like catalytic nanosystem that can display reactive oxygen species (ROS)-manipulating anticancer therapeutic activity. CuAS-PMs were fabricated through metal-catechol chelation-based formation of the CuAS complex on the core domain of poly (ethylene glycol)-b-poly(3,4-dihydroxy-L-phenylalanine) (PEG-PDOPA) copolymer micelles. CuAS-PMs maintained structural robustness under serum conditions. The insoluble state of the CuAS complex was effectively retained at physiological pH, whereas, at endosomal pH, the CuAS complex was ionized to release arsenite and cuprous Fenton catalysts (Cu+ ions). Upon endocytosis, CuAS-PMs simultaneously released hydrogen peroxide (H2O2)-generating arsenite and Fenton-like reaction-catalyzing Cu+ ions in cancer cells, which synergistically elevated the level of highly cytotoxic hydroxyl radicals (•OH), thereby preferentially killing cancer cells. Animal experiments demonstrated that CuAS-PMs could effectively suppress the growth of solid tumors without systemic in vivo toxicity. The design rationale of CuAS-PMs may provide a promising strategy to develop diverse oxidative stress-amplifying agents with great potential in cancer-specific therapy.
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