Chemotherapy is an important modality in cancer treatment. The major challenges of recent works are to improve drug loading, increase selectivity to target cells, and control the precise release of drugs. In the present study, we devised a smart drug carrier, an aptamer/hairpin DNA-gold nanoparticle (apt/hp-Au NP) conjugate for targeted delivery of drugs. The DNA aptamer sgc8c, which possesses strong affinity for protein tyrosine kinase 7 (PTK7), abundantly expressed on the surface of CCRF-CEM (T-cell acute lymphoblastic leukemia) cells, was assembled onto the surface of Au NPs. The repeated d(CGATCG) sequence within the hpDNA on the Au NP surface was used for the loading of the anticancer drug doxorubicin (Dox). After optimization, 25 (±3) sgc8c and 305 (±9) Dox molecules were successfully loaded onto the AuNP (13 nm) surface. The binding capability of apt/hp-Au NP conjugates toward targeted cells was investigated by flow cytometry and atomic absorption spectroscopy, which showed that the aptamer-functionalized nanoconjugates were selective for targeting of cancer cells. A cell toxicity (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, MTT) assay also demonstrated that these drug-loaded nanoconjugates could kill targeted cancer cells more effectively than nontargeted (control) cells. Most importantly, when illuminated with plasmon-resonant light (532 nm), Dox:nanoconjugates displayed enhanced antitumor efficacy with few side effects. The marked release of Dox from these nanoconjugates in living cells was monitored by increasing fluorescence signals upon light exposure. In vitro studies confirmed that aptamer-functionalized hp-Au NPs can be used as carriers for targeted delivery of drugs with remote control capability by laser irradiation with high spatial/temporal resolution.

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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 ultrasoundcontrolled 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/cm 2 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 ultrasoundresponsive 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.