Dual Roles of Graphene Oxide To Attenuate Inflammation and Elicit Timely Polarization of Macrophage Phenotypes for Cardiac Repair
| Autor: | Min-Young Lim, Han Young Kim, Hye-yun Jeong, Gwang Hyeon Eom, Saerom Kong, Youngkeun Ahn, Ju Hee Jun, Mikyung Kang, Jong-Chan Lee, Jooyeon Park, Byung-Soo Kim, Jin Han, Yong Sook Kim, Seungmi Ryu, Yeon Woong Choo, Gun-Jae Jeong |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_treatment Cell Myocardial Infarction General Physics and Astronomy Inflammation 02 engineering and technology Antioxidants 03 medical and health sciences medicine Animals Immunologic Factors Macrophage General Materials Science Cells Cultured chemistry.chemical_classification Mice Inbred BALB C Reactive oxygen species business.industry Macrophages Gene Transfer Techniques General Engineering DNA Genetic Therapy Immunotherapy Macrophage Activation 021001 nanoscience & nanotechnology M2 Macrophage medicine.disease 030104 developmental biology medicine.anatomical_structure chemistry Heart failure Cancer research Graphite Interleukin-4 medicine.symptom Reactive Oxygen Species 0210 nano-technology business Ex vivo |
| Zdroj: | ACS Nano. 12:1959-1977 |
| ISSN: | 1936-086X 1936-0851 |
| DOI: | 10.1021/acsnano.7b09107 |
| Popis: | Development of localized inflammatory environments by M1 macrophages in the cardiac infarction region exacerbates heart failure after myocardial infarction (MI). Therefore, the regulation of inflammation by M1 macrophages and their timely polarization toward regenerative M2 macrophages suggest an immunotherapy. Particularly, controlling cellular generation of reactive oxygen species (ROS), which cause M1 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 M1 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. |
| Databáze: | OpenAIRE |
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