Dual functionalized liposome-mediated gene delivery across triple co-culture blood brain barrier model and specific in vivo neuronal transfection

Bruna dos Santos Rodrigues, Hiroshi Oue, Amrita Banerjee, Takahisa Kanekiyo, Jagdish Singh

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Gene therapy has become a promising approach for neurodegenerative disease treatment, however there is an urgent need to develop an efficient gene carrier to transport gene across the blood brain barrier (BBB). In this study, we strategically designed dual functionalized liposomes for efficient neuronal transfection by combining transferrin (Tf) receptor targeting and enhanced cell penetration utilizing penetratin (Pen). A triple cell co-culture model of BBB confirmed the ability of the liposomes to cross the barrier layer and transfect primary neuronal cells. In vivo quantification of PenTf-liposomes demonstrated expressive accumulation in the brain (12%), without any detectable cellular damage or morphological change. The efficacy of these nanoparticles containing plasmid β-galactosidase in modulating transfection was assessed by β-galactosidase expression in vivo. As a consequence of accumulation in the brain, PenTf-liposomes significantly induced gene expression in mice. Immunofluorescence studies of brain sections of mice after tail vein injection of liposomes encapsulating pDNA encoding GFP (pGFP) illustrate the superior ability of dual-functionalized liposomes to accumulate in the brain and transfect neurons. Taken together, the multifunctional liposomes provide an excellent gene delivery platform for neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)264-278
Number of pages15
JournalJournal of Controlled Release
Volume286
DOIs
StatePublished - Sep 28 2018

Keywords

  • Blood brain barrier
  • Dual-functional liposomes
  • Gene delivery
  • Penetratin
  • Transferrin

ASJC Scopus subject areas

  • Pharmaceutical Science

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