Bioinspired Multivalent Aptamer DNA Nanowires for Cancer Cell-Targeted Therapy

DNA nanowires are a promising carrier for the delivery of anticancer drugs. In vivo application has been hampered by the poor specificity for targeting cancer cells and the susceptibility toward nuclease degradation in biological fluids. Here, we developed a bioinspired multivalent DNA nanowire with active targeting functionality by surrounding periodic aptamer regions for cancer cell-targeted therapy (the system was named BMNW-Apt for simplicity). Our work simplified the design and preparation of DNA nanowires via a dual palindrome-mediated one-step self-assembly strategy. As a result, the periodic aptamers have endowed BMNW-Apt with a multivalent binding effect for cancer cell targeting. The loop-exposed protrusions of H2-Apt form an outer shell to achieve an enhanced resistance under biological fluids, which has made the system ideally suited for target drug delivery. We have demonstrated that BMNW-Apt possesses drug loading, drug-controlled release, low toxicity, outstanding target cell internalization, and tumor enrichment ability. BMNW-Apt@Dox can reduce the toxicity of Dox for nontarget cells and nonfocal tissues. Overall, BMNW-Apt@Dox exhibits an excellent performance for precision cancer therapy. We believe that this simple, efficient strategy provides potential opportunities to build more versatile nanowire-based DNA nanostructures (e.g., DNA dendrimer, three-dimensional (3D) DNA network, and DNA origami).