DNA-conjugated gold nanoparticles for ultrasound targeted drug delivery

Abstract

A novel platform based on gold nanoparticles (Au NPs) coupled with double-stranded DNA sequences and aptamers (referred to as ds(sgc8c)-Au NPs) was developed for ultrasound-controlled targeted drug delivery. The sgc8c aptamers with high affinity to CCRF-CEM (T-cell leukemia) cells facilitated the cellular uptake of ds(sgc8c)-Au NPs. The aptamers were extended with repeated CG base pairs for loading anticancer drugs doxorubicin (Dox). After incubated with ds(sgc8c)-Au NPs for 2 h, the cells were irradiated by 10-MHz high-intensity focused ultrasound (HIFU) at a focal spatial-average temporal-average intensity of 140 W/cm2 for 10 min. It was found that the inertial cavitation induced by HIFU drove the specific release of Dox molecules from ds(sgc8c)-Au NPs as indicated by the increase in Dox fluorescence. The temperature within the focal volume only increased by 3°C during the irradiation, but reducing the gas content in the cell medium resulted in a 50% decrease in the fluorescence enhancement. This system can serve as a novel ultrasound-responsive therapeutic system, showing great promise in targeted drug delivery for remote control of high spatial/temporal resolution as well as reductions in undesirable side effects. © 2012 IEEE.