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Synthesis of Lipidated Ligands and Formulation of Glia-Specific LNPs for RNAi-Mediated BBB Protection.
Xiao, Hai; Bao, Xuemei; Bai, Nuomin; Zhu, Wunile; Saqirila, Saqirila; Hu, Xin; Bao, Qingming; Baigude, Huricha.
Afiliação
  • Xiao H; School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.
  • Bao X; School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.
  • Bai N; School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.
  • Zhu W; School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.
  • Saqirila S; School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.
  • Hu X; School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.
  • Bao Q; School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.
  • Baigude H; School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.
J Med Chem ; 67(15): 13217-13230, 2024 Aug 08.
Article em En | MEDLINE | ID: mdl-39031092
ABSTRACT
Pro-inflammatory polarization of microglia and astrocytes results in neuroinflammation and blood-brain barrier (BBB) disruption after a primary traumatic brain injury (TBI). Herein, we demonstrate that the dual-ligand functionalized lipid nanoparticles (AM31 LNPs) were actively and specifically internalized by microglia and astrocytes via mannose receptor (MR)- and adenosine receptor (AR)-mediated endocytosis, respectively, in a mouse model of TBI. Systemic administration of AM31 LNPs carrying siRNA against p65 resulted in internalization by the glial cells in the peri-infarct region and a robust knockdown of p65 at both mRNA and protein levels in these cells, leading to significant down-regulation of key pro-inflammatory cytokines and up-regulation of key anti-inflammatory cytokines. AM31 LNP-mediated silencing of p65 ameliorated TBI-induced BBB disruption. Our data proved that AM 31 LNP is a promising vehicle for RNA therapeutics for targeting microglia and astrocytes in neural disorder.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Nanopartículas / Lipídeos Limite: Animals Idioma: En Revista: J Med Chem Assunto da revista: QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Nanopartículas / Lipídeos Limite: Animals Idioma: En Revista: J Med Chem Assunto da revista: QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos