Original Article
Chitosan polyplex mediated delivery of miRNA-124 reduces activation of microglial cells in vitro and in rat models of spinal cord injury

https://doi.org/10.1016/j.nano.2015.10.011Get rights and content
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Abstract

Traumatic injury to the central nervous system (CNS) is further complicated by an increase in secondary neuronal damage imposed by activated microglia/macrophages. MicroRNA-124 (miR-124) is responsible for mouse monocyte quiescence and reduction of their inflammatory cytokine production. We describe the formulation and ex vivo transfection of chitosan/miR-124 polyplex particles into rat microglia and the resulting reduction of reactive oxygen species (ROS) and TNF-α and lower expression of MHC-II. Upon microinjection into uninjured rat spinal cords, particles formed with Cy3-labeled control sequence RNA, were specifically internalized by OX42 positive macrophages and microglia cells. Alternatively particles injected in the peritoneum were transported by macrophages to the site of spinal cord injury 72h post injection. Microinjections of chitosan/miR-124 particles significantly reduced the number of ED-1 positive macrophages in the injured spinal cord. Taken together, these data present a potential treatment technique to reduce inflammation for a multitude of CNS neurodegenerative conditions.

From the Clinical Editor

The treatment of spinal cord injury remains an unresolved problem. Secondary damage is often the result of inflammation caused by activated microglia and/or macrophages. In this article, the authors developed their formulation of chitosan/miR-124 polyplex particles and investigated their use in the suppression of neuronal inflammation. This exciting data may provide a new horizon for patients who suffer from spinal cord injury.

Graphical abstract

A chitosan/miRNA-124 nanoparticle was formed and shown to transfect and reduce cytotoxic molecules and activation in classically activated ex vivo microglia. In vivo transfection was seen to be specific to macrophages/microglia in spinal microinjections, and subsequently reduced their activation in microinjection and hemisection models of spinal cord injury.

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Key words

Chitosan polyplex system
miRNA-124
Microglia/macrophage
Inflammation
Spinal cord injury

Cited by (0)

Funding Sources: The authors would like to acknowledge The Lundbeck Foundation Nanomedicine Centre for Individualized Management of Tissue Damage and Regeneration (LUNA), ERA-Net European transnational collaborative project: “Nano-Functionalised Implants for the Regenerative Treatment of Spinal Cord and Nerve Lesions” (Nano4Neuro) and the Swedish Research Council (grant 2014-2306, Medicine and Health) for their support of this research.

Conflict of interest: No.