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.
Bibliographical noteFunding Information:
The authors wish to express their gratefulness to the Health and Labor Sciences Research Grants in Research on Advanced Medical Technology in Nanomedicine Area from the Ministry of Health, Labor and Welfare (MHLW), Japan. Also, they wish to express their thanks to the Project on the Materials Development for Innovative Nano-Drug Delivery Systems from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science