1 research outputs found
Dual Roles of Graphene Oxide To Attenuate Inflammation and Elicit Timely Polarization of Macrophage Phenotypes for Cardiac Repair
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 <i>ex vivo</i> 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 <i>via</i> 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