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

Sasaki, Kentaro; Kogure, Kentaro; Chaki, Shinji; Nakamura, Yoshio; Moriguchi, Rumiko; Hamada, Hirofumi; Danev, Radostin; Nagayama, Kuniaki; Futaki, Shiroh; Harashima, Hideyoshi
August 2008
Analytical & Bioanalytical Chemistry;Aug2008, Vol. 391 Issue 8, p2717
Academic Journal
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.


Related Articles

  • Hepatic Fatty Acid-Binding Proteins of a Teleost, Lateolabrax japonicus. The Primary Structures and Location of a Disulfide Bond1. Odani, Shoji; Baba, Katsuya; Tsuchida, Yutaka; Aoyagi, Yutaka; Wakui, Shuji; Takahashi, Yoshiaki // Journal of Biochemistry;2001, Vol. 129 Issue 1, p69 

    Two fatty acid-binding proteins (FABP), FABP-1 and FABP-2, were purified from the liver cytosol of the teleost, Lateolabrax japonicus (Japan sea bass), and characterized. The complete primary structure of FABP-2 was determined by protein analysis to be the following: MDFSGTWQVY AQENYEEFLR...

  • The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Xian-Ping Dong; Xiping Cheng; Mills, Eric; Delling, Markus; Wang, Fudi; Kurz, Tino; Haoxing Xu // Nature;10/16/2008, Vol. 455 Issue 7215, p992 

    TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4)....

  • The APC protein binds to A/T rich DNA sequences. Deka, Jürgen; Herter, Peter; Sprenger-Haußels, Markus; Koosch, Sonja; Franz, Dorothee; Müller, Klaus-Michael; Kuhnen, Cornelius; Hoffmann, Ingrid; Müller, Oliver // Oncogene;10/7/99, Vol. 18 Issue 41, p5654 

    The tumor suppressor protein APC (Adenomatous Polyposis Coli) is localized in the cytosol and in the nucleus. In this study, we demonstrate that the nuclear APC protein level is high in cells in the basal crypt region of the normal colorectal epithelium. Strikingly, the APC protein staining...

  • Development of synthetic of peptide-functionalized liposome for enhanced targeted ovarian carcinoma therapy. Hong Wu; Li Yao; Jiazhuan Mei; Feng Li // International Journal of Clinical & Experimental Medicine;2014, Vol. 7 Issue 12, p4809 

    In this study, we report an active targeting liposomal formulation directed by a novel peptide (T7) that spe cifically binds to the transferrin receptor (TfR) overexpressed on ovarian carcinoma cells. The objectives of this study were to evaluate the in vitro and in vivo tumor drug targeting...

  • Near Complete Rescue of Experimental Parkinson’s Disease with Intravenous, Non-viral GDNF Gene Therapy. Yun Zhang; William Pardridge // Pharmaceutical Research;May2009, Vol. 26 Issue 5, p1059 

    Abstract Purpose  Rats with experimental Parkinson’s disease (PD) are treated with intravenous glial-derived neurotrophic factor (GDNF) plasmid DNA and non-viral gene therapy using Trojan horse liposomes (THLs) targeted with a monoclonal antibody (MAb) to the rat transferrin...

  • Modulation of Endosomal Escape of IRQ-PEGylated Nano-carrier. Mudhakir, Diky; Akita, Hidetaka; Harashima, Hideyoshi // AIP Conference Proceedings;12/10/2011, Vol. 1415 Issue 1, p67 

    The novel IRQ peptide is one of cell penetrating peptides (CPPs) that has ability to induce endosomal escape. It has been demonstrated that IRQ ligand had ability to facilitate an escape of liposomes encapsulating siRNA from the endosomes presumably by fusion-independent mechanism [1,2]. In the...

  • Sorting nexins provide diversity for retromer-dependent trafficking events. Cullen, Peter J.; Korswagen, Hendrik C. // Nature Cell Biology;Jan2012, Vol. 14 Issue 1, p29 

    Sorting nexins are a large family of evolutionarily conserved phosphoinositide-binding proteins that have fundamental roles in orchestrating cargo sorting through the membranous maze that is the endosomal network. One ancient group of complexes that contain sorting nexins is the retromer. Here...

  • Conjugation to the Cell-Penetrating Peptide TAT Potentiates the Photodynamic Effect of Carboxytetramethylrhodamine. Srinivasan, Divyamani; Muthukrishnan, Nandhini; Johnson, Gregory A.; Erazo-Oliveras, Alfredo; Lim, Jongdoo; Simanek, Eric E.; Pellois, Jean-Philippe // PLoS ONE;2011, Vol. 6 Issue 3, p1 

    Background: Cell-penetrating peptides (CPPs) can transport macromolecular cargos into live cells. However, the cellular delivery efficiency of these reagents is often suboptimal because CPP-cargo conjugates typically remain trapped inside endosomes. Interestingly, irradiation of fluorescently...

  • Lactoferrin in human tumours: immunohistochemical investigations during more than 25 years. Tuccari, Giovanni; Barresi, Gaetano // BioMetals;Oct2011, Vol. 24 Issue 5, p775 

    Lactoferrin (LF) is an iron-binding glycoprotein of the transferrin family, today known to have multifunctional physiological activities. In humans, under normal conditions, LF has been found in blood, mucosal secretions, gastrointestinal fluids, urine and mostly in milk and colostrum. The first...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics