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Synergistic Amplification of Oxidative Stress–Mediated Antitumor Activity via Liposomal Dichloroacetic Acid and MOF‐Fe 2+
Author(s) -
Sun Lei,
Xu Yurui,
Gao Ya,
Huang Xinyu,
Feng Shujun,
Chen Jianmei,
Wang Xuekun,
Guo Leilei,
Li Meng,
Meng Xia,
Zhang Jikang,
Ge Junliang,
An Xueying,
Ding Dang,
Luo Yadong,
Zhang Yu,
Jiang Qing,
Ning Xinghai
Publication year - 2019
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201901156
Subject(s) - dichloroacetic acid , oxidative stress , reactive oxygen species , chemistry , hydrogen peroxide , apoptosis , cancer cell , intracellular , biophysics , biochemistry , cancer , biology , genetics
Cancer cells are susceptible to oxidative stress; therefore, selective elevation of intracellular reactive oxygen species (ROS) is considered as an effective antitumor treatment. Here, a liposomal formulation of dichloroacetic acid (DCA) and metal–organic framework (MOF)‐Fe 2+ (MD@Lip) has been developed, which can efficiently stimulate ROS‐mediated cancer cell apoptosis in vitro and in vivo. MD@Lip can not only improve aqueous solubility of octahedral MOF‐Fe 2+ , but also generate an acidic microenvironment to activate a MOF‐Fe 2+ ‐based Fenton reaction. Importantly, MD@Lip promotes DCA‐mediated mitochondrial aerobic oxidation to increase intracellular hydrogen peroxide (H 2 O 2 ), which can be consequently converted to highly cytotoxic hydroxyl radicals (•OH) via MOF‐Fe 2+ , leading to amplification of cancer cell apoptosis. Particularly, MD@Lip can selectively accumulate in tumors, and efficiently inhibit tumor growth with minimal systemic adverse effects. Therefore, liposome‐based combination therapy of DCA and MOF‐Fe 2+ provides a promising oxidative stress–associated antitumor strategy for the management of malignant tumors.