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Cited by 258

The DOI matches its Crossref record; 111 of the 111 references it cites were found in a registry or an index.

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

Han, Jin, Kim, Yong Sook, Lim, Min-Young, Kim, Han Young, Kong, Saerom, Kang, Mikyung, Choo, Yeon Woong, Jun, Ju Hee, Ryu, Seungmi, Jeong, Hye-yun, Park, Jooyeon, Jeong, Gun-Jae, Lee, Jong-Chan, Eom, Gwang Hyeon, Ahn, Youngkeun, Kim, Byung-Soo·2018·ACS Nano
DOI 10.1021/acsnano.7b09107
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Abstract

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.

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Metadata

Authors
Han, J., Kim, Y. S., Lim, M.-Y., Kim, H. Y., Kong, S., Kang, M., Choo, Y. W., Jun, J. H., Ryu, S., Jeong, H.-Y., Park, J., Jeong, G.-J., Lee, J.-C., Eom, G. H., Ahn, Y., & Kim, B.-S.
Venue
ACS Nano
Publisher
American Chemical Society (ACS)
Published
2018-02-07
Volume
12
Issue
2
Pages
1959-1977
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
DOI
10.1021/acsnano.7b09107
OpenAlex
W2786389763
Cited by
258
References
111
FWCI
8.49
Type
journal article
Language
en
Open access
closed

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