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

研究成果: Article査読

24 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)7960-7970
ページ数11
ジャーナルBiomaterials
34
32
DOI
出版ステータスPublished - 2013 10

ASJC Scopus subject areas

  • バイオエンジニアリング
  • セラミックおよび複合材料
  • 生物理学
  • 生体材料
  • 材料力学

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