1. Academic Validation
  2. Regulation of microglia polarization via mannose receptor-mediated delivery of siRNA by ligand-functionalized DoGo LNP

Regulation of microglia polarization via mannose receptor-mediated delivery of siRNA by ligand-functionalized DoGo LNP

  • RSC Adv. 2021 Oct 4;11(52):32549-32558. doi: 10.1039/d1ra04293a.
Hai Xiao 1 Shuqin Han 1 Huricha Baigude 1
Affiliations

Affiliation

  • 1 Institute of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University Hohhot Inner Mongolia 010020 P. R. China hbaigude@imu.edu.cn +86 471 4992511 +86 471 4992511.
Abstract

The pro-inflammatory polarization of microglia after stroke is one of the major causes of secondary brain injury. Downregulation of the gene involved in canonical inflammatory pathways in glial cells can exert neuroprotective effects via inhibiting the release of pro-inflammatory factors. In this study, we functionalized DoGo lipids with mannose, the ligand of the Mannose Receptor (MR) that is expressed in microglia, and evaluated the MR-mediated cellular internalization of DoGo lipid nanoparticles (denote M3) carrying siRNA against TLR4 in BV2 cells in vitro. We confirmed that siTLR4/M3 complexes were specifically internalized by BV2 cells in a MR-dependent manner, and the treatment of oxygen glucose deprivation (OGD)-treated BV2 cells with siTLR4/M3 complexes resulted in remarkable silencing of TLR4, and induced downregulated M1 polarization and upregulated M2 polarization markers. Collectively, our data suggest that the M3 lipoplex is a promising microglia-targeting siRNA delivery agent.

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