Radiolytic reduction characteristics of drug-encapsulating DNA aggregates possessing disulfide bond.
Radiation-responsive aggregates consisting of artificial DNA were demonstrated. We prepared DNA amphiphiles (DAMs) consisting of oligodeoxynucleotides (ODNs) as the hydrophilic part and an alkyl chain as the hydrophobic part, which were linked by a radiation-sensitive disulfide bond. DAMs assembled to form nanosized aggregates in aqueous solution that encapsulated hydrophobic dyes and drugs. X-irradiation, which triggered selective reduction at the disulfide bond in the DAMs, induced an exchange reaction, resulting in dissociation of the aggregates and release of encapsulated dyes and drugs. Among the DAMs synthesized in this study, DAM 1 possessing 5 mer ODNs showed favorable properties as a nanocarrier; for example, the large amount of drug was encapsulated in the aggregates consisting of DAM 1, and the aggregates showed the high sensitivity to radiolytic reduction. Biological experiments using living A549 cells revealed that the aggregates smoothly penetrated into the cells without the need for transfection reagents, while the drugs inside the aggregates were inert because of the encapsulation. X-irradiation enhanced the cytotoxicity because of dissociation of the aggregates and concomitant release of drugs.
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510, Japan. tanabeka@scl.kyoto-u.ac.jp
Kazuhito
K
Tanabe
Takumi
T
Asada
Takeo
T
Ito
Sei-ichi
S
Nishimoto
D002626:Chemistry, Pharmaceutical; D004247:DNA / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization
D004220:Disulfides; D004247:DNA