Gene delivery to dendritic cells mediated by complexes of lipoplexes and pH-sensitive fusogenic polymer-modified liposomes.
Dendritic cells (DCs) are potent professional antigen presenting cells that are useful for cancer immunotherapy. We previously reported the preparation and characterization of complexes of lipoplexes with pH-sensitive fusogenic liposomes, which comprise polymers based on poly(glycidol) with carboxyl groups, to transfect various malignant cell lines. The present study applied this kind of vectors to transfection of a murine DC line DC2.4. We first optimized the ratios of their components for efficient transfection. We subsequently investigated the effects of ligands and pH-sensitive polymers to improve transfection activities. Our results indicate that the anionic surface derived from pH-sensitive polymers might be recognized by scavenger receptors on DC2.4 cells. In addition, no effects on transfection or cell association were observed by attaching ligands such as transferrin and mannan. We found that more sensitive pH-responding polymers led to higher transfection activities into DC2.4 cells, which suggest that endosomal escape is important for transfection into DC2.4 cells. These complexes with pH-sensitive fusogenic polymers exhibited higher transfection activity toward DC2.4 cells than some commercial reagents and hence may be useful as a gene vector for DCs.
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan.
Eiji
E
Yuba
Chie
C
Kojima
Naoki
N
Sakaguchi
Atsushi
A
Harada
Kazunori
K
Koiwai
Kenji
K
Kono
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics; D001550:Benzamidines / Q000737:chemistry; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D051379:Mice; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry; D014162:Transfection
C450860:3,5-dipentadecyloxybenzamidine hydrochloride; D000951:Antigens, Neoplasm; D001550:Benzamidines; D005227:Fatty Acids; D015395:Histocompatibility Antigens Class I; D008081:Liposomes; D011108:Polymers; D011409:Propylene Glycols; C502907:polyglycidol; D049452:Green Fluorescent Proteins; D008156:Luciferases