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

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.