The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain

Ji yun Huang, Ying mei Lu, Huan Wang, Jun Liu, Mei hua Liao, Ling juan Hong, Rong rong Tao, Muhammad Masood Ahmed, Ping Liu, Shuang shuang Liu, Kohji Fukunaga, Yong zhong Du, Feng Han

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Nanocarrier-based drug delivery systems have attracted wide interest for the treatment of brain disease. However, neurotoxicity of nanoparticle has limited their therapeutic application. Here we demonstrated that lipid nanoparticles (LNs) accumulated in the brain parenchyma within 3h of intravenous injection to mice and persisted for more than 24 weeks, coinciding with a dramatic activation of brain microglia. Morphological characteristic of microglial activation also observed in LNs-treated Cx3cr1GFP/+ mice. Invivo study with two-photon confocal microscopy revealed abnormal Ca2+ waves in microglia following LNs injection. The correlated activation of caspase-1, IL-1β and neurovascular damage following LNs injection was attenuated in P2X7-/- mice. PEGylation of LNs reduced correlated nanoparticles aggregation. Moreover, PEGylation of LNs ameliorated the P2X7/caspase-1/IL-1β signalling-dependent microglia activation and neurovascular damage. In conclusion, PEGylation of LNs is a promising biomaterial for brain-targeted therapy that inhibits P2X7-dependent neuroinflammatory response.

Original languageEnglish
Pages (from-to)7960-7970
Number of pages11
JournalBiomaterials
Volume34
Issue number32
DOIs
Publication statusPublished - 2013 Oct 1

Keywords

  • Brain
  • Lipid nanoparticles
  • Microglia
  • Neuroinflammatory response
  • P2X receptor
  • PEGylation

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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