Gold Nanoclusters as Smart Nanoplatforms for Targeted Cancer Therapy

Gold nanoclusters (AuNCs), known for their biocompatibility, intrinsic fluorescence, and magnetic properties represent an interesting nanomaterial for targeted drug delivery. Herein, a multifunctional platform is designed based on AuNCs modified with DNA strands for the loading and triggered release of doxorubicin (Dox), a chemotherapeutic agent. The surface of these nanoclusters is initially modified with a DNA strand and subsequently hybridized with a complementary DNA strand functionalized with folic acid (FA). The modification with FA facilitates targeted drug delivery to MCF‐7 cells. The DNA on the AuNCs surface allows for the capture of Dox via intercalation. Cellular uptake and cytotoxicity are assessed in 2D cell culture and spheroid models. The results demonstrate a significantly higher uptake of the targeted AuNCs into MCF‐7 cells compared to nontargeted counterparts. Moreover, under radiofrequency (RF) irradiation, the targeted AuNCs exhibit increased cytotoxicity. This cytotoxicity can be attributed to multiple factors, including hyperthermia induced by RF irradiation, heat‐triggered release of the loaded drug, and the generation of reactive oxygen species (ROS). This research sheds light on the promising applications of AuNCs in cancer therapy, leveraging their unique properties for precise and effective treatment strategies.