Dual Roles of Graphene Oxide To Attenuate Inflammation and Elicit Timely Polarization of Macrophage Phenotypes for Cardiac Repair

被引:209
作者
Han, Jin [1 ]
Kim, Yong Sook [2 ]
Lim, Min-Young [1 ]
Kim, Han Young [1 ]
Kong, Saerom [1 ]
Kang, Mikyung [3 ]
Choo, Yeon Woong [1 ]
Jun, Ju Hee [4 ]
Ryu, Seungmi [3 ]
Jeong, Hye-yu [4 ]
Park, Jooyeon [1 ]
Jeong, Gun-Jae [1 ]
Lee, Jong-Chan [1 ]
Eom, Gwang Hyeon [5 ]
Ahn, Youngkeun [4 ,6 ,7 ]
Kim, Byung-Soo [1 ,3 ,8 ]
机构
[1] Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 08826, South Korea
[2] Chonnam Natl Univ Hosp, Biomed Res Inst, Gwangju 61469, South Korea
[3] Seoul Natl Univ, Interdisciplinary Program Bioengn, Seoul 08826, South Korea
[4] Chonnam Natl Univ Hosp, Cell Regenerat Res Ctr, Gwangju 61469, South Korea
[5] Chonnam Natl Univ, Sch Med, Dept Pharmacol, Gwangju 61469, South Korea
[6] Chonnam Natl Univ Hosp, Dept Cardiol, Gwangju 61649, South Korea
[7] Chonnam Natl Univ, Sch Med, PLUS Ctr Creat Biomed Scientists BK21, 160 Baekseo Ro, Gwangju 61469, South Korea
[8] Seoul Natl Univ, Inst Chem Proc, Seoul 08826, South Korea
基金
新加坡国家研究基金会;
关键词
cardiac repair; graphene oxide; immune modulatory; macrophage; myocardial infarction; MESENCHYMAL STEM-CELLS; MYOCARDIAL-INFARCTION; IN-VITRO; ACTIVATED MACROPHAGES; ANTIINFLAMMATORY PROPERTIES; THERAPEUTIC-EFFICACY; ANTIOXIDANT ACTIVITY; OXIDATIVE STRESS; PROGENITOR CELLS; DELIVERY-SYSTEM;
D O I
10.1021/acsnano.7b09107
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Development of localized inflammatory environments by MI macrophages in the cardiac infarction region exacerbates heart failure after myocardial infarction (MI). Therefore, the regulation of inflammation by Ml macrophages and their timely polarization toward regenerative M2 macrophages suggest an immunotherapy. Particularly, controlling cellular generation of reactive oxygen species (ROS), which cause MI differentiation, and developing M2 macrophage phenotypes in macrophages propose a therapeutic approach. Previously, stem or dendritic cells were used in MI for their anti-inflammatory and cardioprotective potentials and showed inflammation modulation and M2 macrophage progression for cardiac repair. However, cell-based therapeutics are limited due to invasive cell isolation, time-consuming cell expansion, labor-intensive and costly ex vivo cell manipulation, and low grafting efficiency. Here, we report that graphene oxide (GO) can serve as an antioxidant and attenuate inflammation and inflammatory polarization of macrophages via reduction in intracellular ROS. In addition, GO functions as a carrier for interleukin-4 plasmid DNA (IL-4 pDNA) that propagates M2 macrophages. We synthesized a macrophage-targeting/polarizing GO complex (MGC) and demonstrated that MGC decreased ROS in immune-stimulated macrophages. Furthermore, DNA-functionalized MGC (MGC/IL-4 pDNA) polarized MI to M2 macrophages and enhanced the secretion of cardiac repair-favorable cytokines. Accordingly, injection of MGC/IL-4 pDNA into mouse MI models attenuated inflammation, elicited early polarization toward M2 macrophages, mitigated fibrosis, and improved heart function. Taken together, the present study highlights a biological application of GO in timely modulation of the immune environment in MI for cardiac repair. Current therapy using off-the-shelf material GO may overcome the shortcomings of cell therapies for MI.
引用
收藏
页码:1959 / 1977
页数:37
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