Efficient cytoplasmic protein delivery by means of a multifunctional envelope-type nano device.
The potential for protein therapy, such as the use of antibodies, and vaccines is now well accepted. However, it is difficult to enhance efficiency in protein therapy without a suitable delivery system for delivering proteins to target sites. Here we describe the development of protein delivery system, which is capable of cytoplasmic delivery as well as efficient packaging. The multifunctional envelope-type nano device (MEND), which was originally developed for the delivery of nucleic acids such as plasmid DNA and oligodeoxynucleotides, can also be applied to protein delivery. In this study, the green fluorescent protein (GFP), a model protein, was condensed with stearyl octaarginine (stearyl R8) to form a nano particle, which was then coated with a lipid membrane, thus permitting R8 to be introduced for efficient cellular uptake and controlled intracellular trafficking. The packaging efficiency of the MEND was significantly higher than that of conventional liposomes, because the GFP can be encapsulated a condensed form. According to confocal laser scanning microscopy, the MEND is internalized efficiently and escapes from the acidic compartment to efficiently release GFP into the cytosol. These results indicate that the MEND can serve as a useful cytoplasmic delivery system for protein therapy.
Suzuki
Ryosuke
R
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Yamada
Yuma
Y
Harashima
Hideyoshi
H
D003593:Cytoplasm / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D010316:Particle Size; D010957:Plasmids / Q000187:drug effects / Q000235:genetics; D011506:Proteins / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013228:Stearates / Q000737:chemistry
D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D011506:Proteins; D011993:Recombinant Fusion Proteins; D013228:Stearates; D049452:Green Fluorescent Proteins; D004247:DNA