Abstract
The control of gene transfection in the body is a core issue in gene therapy. Photochemical internalization is a technology that allows light-induced delivery of DNA, drugs or other biological factors directly inside cells. Usually it requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. Here we present a system for in vivo DNA delivery in which these two components are assembled into one structure. This is a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer phthalocyanine, which provides the photosensitizing action. The ternary complex showed more than 100-fold photochemical enhancement of transgene expression in vitro with reduced photocytotoxicity. In an animal experiment, subconjuctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site. This work demonstrates a new biomedical application for dendrimers, and the first success in the photochemical-internalization-mediated gene delivery in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 934-941 |
| Number of pages | 8 |
| Journal | Nature materials |
| Volume | 4 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2005 Dec |
Bibliographical note
Funding Information:We thank N. Kanayama (the University of Tokyo), S. Kawauchi (National Defense Medical College) and K. Date (the University of Tokyo) for technical assistance. This work was supported in part by the Core Research Program for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency (JST). Correspondence and requests for materials should be addressed to K.K.3 Supplementary Information accompanies this paper on www.nature.com/naturematerials.
All Science Journal Classification (ASJC) codes
- Chemistry(all)
- Materials Science(all)
- Condensed Matter Physics
- Mechanics of Materials
- Mechanical Engineering