TY - JOUR
T1 - Dual functionalized liposome-mediated gene delivery across triple co-culture blood brain barrier model and specific in vivo neuronal transfection
AU - dos Santos Rodrigues, Bruna
AU - Oue, Hiroshi
AU - Banerjee, Amrita
AU - Kanekiyo, Takahisa
AU - Singh, Jagdish
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/9/28
Y1 - 2018/9/28
N2 - 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.
AB - 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.
KW - Blood brain barrier
KW - Dual-functional liposomes
KW - Gene delivery
KW - Penetratin
KW - Transferrin
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U2 - 10.1016/j.jconrel.2018.07.043
DO - 10.1016/j.jconrel.2018.07.043
M3 - Article
C2 - 30071253
AN - SCOPUS:85050990616
SN - 0168-3659
VL - 286
SP - 264
EP - 278
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -