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J. Control. Release, Vol 361, Sep 2023, Pages 350-360 | https://doi.org/10.1016/j.jconrel.2023.07.050 Ferritin-nanocaged copper arsenite minerals with oxidative stress-amplifying activity for targeted cancer therapy

Kyung Kwan Lee ^a,b, Jong-Won Kim ^a, Chang-Soo Lee ^a,c, Sang Cheon Lee^d

^aBionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
^bDepartment of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
^cDepartment of Biotechnology, University of Science & Technology (UST), Daejeon 34113, Republic of Korea
^dDepartment of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea

Corresponding authors: Chang-Soo Lee, Sang Cheon Lee

Abstract

We report copper(II) arsenite-encapsulated ferritin nanoparticles (CuAS-FNs) as oxidative stress-amplifying anticancer agents. The CuAS-FNs were fabricated through CuAS mineralization in the cavity of the FNs. The formation of crystalline CuAS complex minerals in the FNs was systematically identified using various analytical tools, including X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM)-associated energy-dispersive X-ray spectroscopy (TEM-EDS). The CuAS-FNs showed pH-dependent release behavior, in which the CuAS mineral was effectively retained at physiological pH, in contrast, at lysosomal pH, the CuAS complex was dissociated to release arsenite and Cu2+ ions. At lysosomal pH, the release rate of arsenite (HAsO32−) and Cu2+ ions from the CuAS-FNs more accelerated than at physiological pH. Upon transferrin receptor-1-mediated endocytosis, the CuAS-FNs simultaneously released arsenite and Cu2+ ions in cells. The released arsenite ions can increase the intracellular concentration of hydrogen peroxide (H2O2), with which the Cu2+ ions can elevate the level of hydroxyl radicals (·OH) via Fenton-like reaction. Thus, the CuAS-FNs could target cancer cell through the recognizing ability of FNs and kill cancer cells by amplifying the ·OH level through the synergistic activity of Cu2+ and arsenic ions. Importantly, MCF-7 tumors were effectively suppressed by CuAS-FNs without systemic in vivo toxicity. Therefore, the CuAS-FNs is a promising class of Fenton-like catalytic nanosystem for cancer treatment.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-08-11)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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