TY - JOUR
T1 - Functionalized liposomal nanoparticles for efficient gene delivery system to neuronal cell transfection
AU - dos Santos Rodrigues, Bruna
AU - Banerjee, Amrita
AU - Kanekiyo, Takahisa
AU - Singh, Jagdish
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/7/20
Y1 - 2019/7/20
N2 - Liposome based delivery systems provide a promising strategy for treatment of neurodegenerative diseases. A rational design of brain-targeted liposomes can support the development of more efficient treatments with drugs and gene materials. Here, we characterized surface modified liposomes with transferrin (Tf) protein and penetratin (Pen), a cell-penetrating peptide, for efficient and targeted gene delivery to brain cells. PenTf-liposomes efficiently encapsulated plasmid DNA, protected them against enzymatic degradation and exhibited a sustained in vitro release kinetics. The formulation demonstrated low cytotoxicity and was non-hemolytic. Liposomes were internalized into cells mainly through energy-dependent pathways especially clathrin-mediated endocytosis. Reporter gene transfection and consequent protein expression in different cell lines were significantly higher using PenTf-liposomes compared to unmodified liposomes. The ability of these liposomes to escape from endosomes can be an important factor which may have likely contributed to the high transfection efficiency observed. Rationally designed bifunctional targeted-liposomes provide an efficient tool for improving the targetability and efficacy of synthesized delivery systems. This investigation of liposomal properties attempted to address cell differences, as well as, vector differences, in gene transfectability. The findings indicate that PenTf-liposomes can be a safe and non-invasive approach to transfect neuronal cells through multiple endocytosis pathways.
AB - Liposome based delivery systems provide a promising strategy for treatment of neurodegenerative diseases. A rational design of brain-targeted liposomes can support the development of more efficient treatments with drugs and gene materials. Here, we characterized surface modified liposomes with transferrin (Tf) protein and penetratin (Pen), a cell-penetrating peptide, for efficient and targeted gene delivery to brain cells. PenTf-liposomes efficiently encapsulated plasmid DNA, protected them against enzymatic degradation and exhibited a sustained in vitro release kinetics. The formulation demonstrated low cytotoxicity and was non-hemolytic. Liposomes were internalized into cells mainly through energy-dependent pathways especially clathrin-mediated endocytosis. Reporter gene transfection and consequent protein expression in different cell lines were significantly higher using PenTf-liposomes compared to unmodified liposomes. The ability of these liposomes to escape from endosomes can be an important factor which may have likely contributed to the high transfection efficiency observed. Rationally designed bifunctional targeted-liposomes provide an efficient tool for improving the targetability and efficacy of synthesized delivery systems. This investigation of liposomal properties attempted to address cell differences, as well as, vector differences, in gene transfectability. The findings indicate that PenTf-liposomes can be a safe and non-invasive approach to transfect neuronal cells through multiple endocytosis pathways.
KW - Bifunctional liposome
KW - Brain targeting
KW - Gene delivery
KW - Penetratin
KW - Transferrin
UR - http://www.scopus.com/inward/record.url?scp=85067390527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067390527&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2019.06.026
DO - 10.1016/j.ijpharm.2019.06.026
M3 - Article
C2 - 31202901
AN - SCOPUS:85067390527
SN - 0378-5173
VL - 566
SP - 717
EP - 730
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
ER -