PEGylated gene nanocarriers based on block catiomers bearing ethylenediamine repeating units directed to remarkable enhancement of photochemical transfection.
The therapeutic usefulness of macromolecular drugs such as plasmid DNA is often limited by the inefficient transfer of macromolecules to the cytosol. Photochemical internalization (PCI) technology, in which the endosomal escape of DNA or its complex is assisted by co-incubated photosensitizers that photodamage endosome membrane, offers a solution for this problem. A series of poly(ethylene glycol) (PEG)-based block polycatiomers with increasing number of ethylenediamine repeating unit at side chain of polycatiomers were complexed with pDNA to form the PEGylated polyplexes as a biocompatible gene carrier. Dendrimeric phthalocyanine (DPc)-incorporated micelle was used to assist the gene transfer of these polyplexes in a light-inducible manner. As a result, the light-inducible transfection activity was significantly enhanced as the number of amino group at the side chain of PEG-b-polycatiomer increased. The polyplex from PEG-b-polycatiomer having the longest ethylenediamine structure achieved approximately 1000-fold enhancement of transfection upon photoirradiation. This result supports the underlying hypothesis that photochemical transfection and proton sponge effect of polycations can work synergistically to enhance the transfection efficiency. With careful balance between photochemical transfection enhancement and cytotoxicity, PEG-b-polycatiomers used in this study might be a potential candidate for in vivo PCI-mediated gene transfer.
Arnida
Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Nishiyama
Nobuhiro
N
Kanayama
Naoki
N
Jang
Woo-Dong
WD
Yamasaki
Yuichi
Y
Kataoka
Kazunori
K
D000465:Algorithms; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004337:Drug Carriers; D004996:Ethidium; D005029:Ethylenediamines / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D007202:Indicators and Reagents; D017078:Laser-Doppler Flowmetry; D008027:Light; D008823:Micelles; D053758:Nanoparticles; D010777:Photochemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D012542:Scattering, Radiation; D014162:Transfection
D004337:Drug Carriers; D005029:Ethylenediamines; D007202:Indicators and Reagents; D008823:Micelles; D011092:Polyethylene Glycols; D004247:DNA; D004996:Ethidium