title: Cationic liposome-mediated gene delivery: biophysical study and mechanism of internalization.
abstract: To identify factors affecting cationic liposome-mediated gene delivery efficiency, we studied the relationship between the biophysical characteristics of liposome/DNA complexes (lipoplexes) at different (+/-) charge ratios, their structures as monitored by atomic force microscopy (AFM), and their mechanism(s) of internalization into the cells. Significant changes were observed in the particle size and zeta potential of liposomes and their structures assessed by AFM upon addition of DNA, which depended on (+/-) charge ratios. AFM images showed that lipoplexes were formed from extensively fused and apparently homogeneous lipid particles encapsulating DNA. Lipoplexes were found to internalize the cells through the endocytosis pathway. Lipoplex-cell fusion was found to occur mainly at the plasma membrane level; however, this lipoplex-cell membrane fusion was found to be essential for the uptake of the large particles. A new perspective for the internalization of large lipoplex particles into cytoplasm is discussed.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Tokushima, Shomachi 1, Tokushima 770-8505, Japan.
authors.forename: Mohamad Radwan
authors.initials: MR
authors.lastname: Almofti
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Ammar
authors.initials: A
authors.lastname: Almofti
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Baba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiwada
mesh_terms: D055592:Biophysical Phenomena; D001703:Biophysics; D002412:Cations; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004705:Endocytosis; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D008055:Lipids; D008081:Liposomes / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D010957:Plasmids / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D002412:Cations; D008055:Lipids; D008081:Liposomes; D004247:DNA