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 [email protected]@Apt). Targeted antitumor drug delivery system [email protected]@[email protected] 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 [email protected]@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 [email protected]@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 [email protected]@[email protected] 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 [email protected]@Apt nanocomposite possesses low cytotoxicity to MCF-7 cell in a wide concentration range of 5–50 μg 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 [email protected]@[email protected] can be a promising targeted drug delivery platform for cancer therapy.