An artificial virus-like nano carrier system: enhanced endosomal escape of nanoparticles via synergistic action of pH-sensitive fusogenic peptide derivatives.
We previously reported that transferrin (Tf)-modified liposomes (Tf-L) additionally modified with a cholesterylated pH-sensitive fusogenic peptide (Chol-GALA) can release an encapsulated aqueous phase marker to cytosol via endosomal membrane fusion. However, further obstacles need to be overcome to bring the Tf-L to the level of a viral-like gene delivery system. In this study, we developed a novel packaging method to encapsulate condensed plasmid DNA into PEgylated Tf-L (Tf-PEG-L) to form a core-shell-type nanoparticle. The most difficult challenge was to provide a mechanism of escape for the condensed core from endosome to cytosol in the presence of polyethylene glycol (PEG). We hypothesized that a membrane-introduced Chol-GALA and a PEgylated GALA would interact synergistically to induce membrane fusion between liposome and endosome. By simultaneously incorporating Chol-GALA into the membrane of Tf-PEG-L and GALA at tips of PEG chains, a condensed core was released into cytosol, and transfection activity increased 100-fold. We concluded that topological control was responsible for the synergistic effect of GALA derivatives introduced on Tf-PEG-L.
Sasaki
Kentaro
K
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.
Kogure
Kentaro
K
Chaki
Shinji
S
Nakamura
Yoshio
Y
Moriguchi
Rumiko
R
Hamada
Hirofumi
H
Danev
Radostin
R
Nagayama
Kuniaki
K
Futaki
Shiroh
S
Harashima
Hideyoshi
H
D002784:Cholesterol / Q000737:chemistry; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020014:K562 Cells; D008561:Membrane Fusion; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism; D022701:Virosomes / Q000737:chemistry* / Q000378:metabolism
D010455:Peptides; D014168:Transferrin; D022701:Virosomes; C066951:GALA peptide; D011092:Polyethylene Glycols; D002784:Cholesterol