DNA‐Au Nanomachine Equipped with i‐Motif and G‐Quadruplex for Triple Combinatorial Anti‐Tumor Therapy

Abstract In the present study, the design, construction, and operation of a functional DNA‐decorated dynamic gold (Au) nanomachine as a therapeutic agent for triple combinatorial anti‐cancer therapy are revealed. Taking advantage of the intrinsic optical properties of Au nanoparticles, which depend on their size, a cytosine rich i‐motif sequence is employed for intracellular pH‐sensitive duplex dissociation and subsequent aggregation of the DNA‐Au nanomachine, enabling anticancer drug release and photothermal ablation upon irradiation with infrared light. Moreover, another functional DNA sequence, a G‐quadruplex, is exploited for the stable loading and intracellular delivery of a photosensitizer to achieve effective photodynamic therapy under red light illumination. The G‐quadruplex‐assisted enhanced reactive oxygen species generation, pH‐responsive dynamic aggregation behavior, consequent drug release, and the photothermal effect are investigated. Furthermore, the combinatorial chemo, photodynamic, and photothermal therapeutic effects of the functional DNA‐decorated Au nanomachines are evaluated in vitro and in vivo using a triple negative breast cancer model.