Enhanced laminin-derived peptide AG73-mediated liposomal gene transfer by bubble liposomes and ultrasound.
A promising strategy as a cancer therapeutic is tumor-targeted gene delivery. The AG73 peptide derived from the laminin alpha1 chain is a ligand for syndecans, and syndecan-2 is highly expressed in some cancer cells. In this study, AG73-PEG liposomes were developed for selective gene delivery to syndecan-2 overexpressing cancer cells. AG73-PEG liposomes were used in combination with Bubble liposomes and ultrasound exposure to enhance transfection efficiency by promoting the escape of the liposomes from the endosome to the cytosol. AG73-PEG liposomes showed selective gene delivery to syndecan-2 overexpressing cancer cells. Furthermore, AG73-mediated liposomal gene transfection efficiency was enhanced by 60-fold when Bubble liposomes and ultrasound exposure were used, despite the absence of an increase in the uptake of AG73-PEG liposomes into the cells. Confocal microscope analysis revealed that the Bubble liposomes and ultrasound promoted intracellular trafficking of the AG73-PEG liposomes during gene transfection. Thus, the combination of AG73-PEG liposomes with Bubble liposomes and ultrasound exposure may be a promising method to achieve selective and efficient gene delivery for cancer therapy.
Negishi
Yoichi
Y
Drug and Gene Delivery Systems, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. negishi@ps.toyaku.ac.jp
Omata
Daiki
D
Iijima
Hiroshi
H
Takabayashi
Yasuko
Y
Suzuki
Kentaro
K
Endo
Yoko
Y
Suzuki
Ryo
R
Maruyama
Kazuo
K
Nomizu
Motoyoshi
M
Aramaki
Yukihiko
Y
D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007797:Laminin / Q000008:administration & dosage / Q000737:chemistry; D008081:Liposomes; D045423:Microbubbles; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011092:Polyethylene Glycols; D053669:Syndecan-2 / Q000378:metabolism; D014162:Transfection; D014465:Ultrasonics
D007797:Laminin; D008081:Liposomes; D010455:Peptides; D053669:Syndecan-2; C084098:laminin A; D011092:Polyethylene Glycols