Synergistic Amplification of Oxidative Stress–Mediated Antitumor Activity via Liposomal Dichloroacetic Acid and MOF‐Fe2+. Issue 24 (9th May 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Small. Volume 15:Issue 24(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-05-09
• Subjects: antitumor treatment -- dichloroacetic acid -- liposomes -- MOF‐Fe2+ -- oxidative stress; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201901156
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: 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 (H2 O2 ), 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. Abstract : A liposomal formulation of metal–organic framework (MOF)‐Fe 2+ and dichloroacetic acid (DCA), named MD@Lip, is developed for improving reactive oxygen species‐based anticancer treatment. MD@Lip can not only stimulate DCA‐mediated H2 O2 generation, but also effectively promote MOF‐Fe 2+ ‐associated Fenton reaction to produce cytotoxic hydroxyl radicals, thereby inducing cancer cell apoptosis and inhibiting tumor growth with negligible adverse effects.