Aptamer-templated silver nanoclusters embedded in zirconium metal-organic framework for targeted antitumor drug delivery

In this study, we reported a targeted antitumor drug delivery system (DDS) based on the nanocomposite of zirconium metal-organic framework (Zr-MOF, UiO-66) embedded with bioactive silver nanoclusters (Ag NCs) by using AS1411 aptamer (Apt) as the template (denoted by UiO-66@AgNCs@Apt). Targeted antitumor drug delivery system UiO-66@AgNCs@Apt@DOX was also obtained by one-pot encapsulation of antitumor drug doxorubicin (DOX) and formation of Ag NCs, which showed higher DOX loading efficiency and sustained controlled release than the UiO-66@AgNCs@Apt/DOX formed by two separate processes. A proof-of-principle targeting specificity study conducted by confocal laser scanning microscopy reveals that AS1411 aptamer-modified UiO-66@AgNCs@Apt can be effectively taken up and internalized by target cancer cells with high selectivity. In vitro cellular uptake and drug delivery study were further compared for both cancer MCF-7 and normal L929 cells to validate the enhanced tumor-targeted delivery of DOX. The results show that UiO-66@AgNCs@Apt@DOX can be internalized by AS1411-mediated endocytosis, and the released DOX can be effectively delivered to the nucleus, which can serve as in vivo targeted drug delivery system. Cell viability assay illustrates that the synthesized UiO-66@AgNCs@Apt nanocomposite possesses low cytotoxicity to MCF-7 cell in a wide concentration range of 5-50 mu g mL(-1), and the drug formulations exhibit good capability for targeted DOX delivery and intracellular controlled release, leading to a robust and enhanced antitumor effect in vitro. These results prove that the proposed AS1411-functionalized UiO-66@AgNCs@Apt@DOX can be a promising targeted drug delivery platform for cancer therapy.