TITLE

An artificial virus-like nano carrier system: enhanced endosomal escape of nanoparticles via synergistic action of pH-sensitive fusogenic peptide derivatives

AUTHOR(S)
Sasaki, Kentaro; Kogure, Kentaro; Chaki, Shinji; Nakamura, Yoshio; Moriguchi, Rumiko; Hamada, Hirofumi; Danev, Radostin; Nagayama, Kuniaki; Futaki, Shiroh; Harashima, Hideyoshi
PUB. DATE
August 2008
SOURCE
Analytical & Bioanalytical Chemistry;Aug2008, Vol. 391 Issue 8, p2717
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 acitivty increased 100-fold. We concluded that topological control was responsible for the synergistic effect of GALA derivatives introduced on Tf-PEG-L.
ACCESSION #
33337106

 

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