Graphene oxide as a potential drug carrier - Chemical carrier activation, drug attachment and its enzymatic controlled release.

Abstract

Graphene oxide (GO), due to its properties, such as nanometric dimensions, large specific surface area, and biocompatibility, can be used as a carrier in controlled drug release systems. The method of its chemical activation before drug molecules binding was elaborated. Doxorubicin (DOX), an anticancer drug, was attached to the surface of GO via the Gly-Gly-Leu linker. Approximately 3.07·1020 molecules of the tripeptide were attached to 1g of GO and subsequently almost the same number of DOX molecules. GO was suspended inside a sol surrounded by a thin porous membrane. The bound DOX was effectively released using thermolysin, an enzyme cleaving peptide bonds between Gly and Leu inside the linker structure. The membrane, as the shell was responsible for keeping enzyme molecules in their native form and GO flakes inside the carrier, simultaneously allowed the released drug molecules to diffuse outside. The rate of drug release was described as a function of the enzyme concentration and mass of DOX expressed on carrier volume; thus, the daily dose and length of the therapy can be controlled. Studies involving the cell line of mice fibrosarcoma WEHI 164 have shown that the prepared carrier itself is not toxic and only the introduction of DOX-releasing enzyme into it causes cell death.