Signal‐amplified imaging of microRNAs (miRNAs) is a promising strategy at the single‐cell level because liquid biopsy fails to reflect real‐time dynamic miRNA levels. However, the internalization pathways for available conventional vectors predominantly involve endo‐lysosomes, showing nonideal cytoplasmic delivery efficiency. In this study, size‐controlled 9‐tile nanoarrays are designed and constructed by integrating catalytic hairpin assembly (CHA) with DNA tile self‐assembly technology to achieve caveolae‐mediated endocytosis for the amplified imaging of miRNAs in a complex intracellular environment. Compared with classical CHA, the 9‐tile nanoarrays possess high sensitivity and specificity for miRNAs, achieve excellent internalization efficiency by caveolar endocytosis, bypassing lysosomal traps, and exhibit more powerful signal‐amplified imaging of intracellular miRNAs. Because of their excellent safety, physiological stability, and highly efficient cytoplasmic delivery, the 9‐tile nanoarrays can realize real‐time amplified monitoring of miRNAs in various tumor and identical cells of different periods, and imaging effects are consistent with the actual expression levels of miRNAs, ultimately demonstrating their feasibility and capacity. This strategy provides a high‐potential delivery pathway for cell imaging and targeted delivery, simultaneously offering a meaningful reference for the application of DNA tile self‐assembly technology in relevant fundamental research and medical diagnostics.
Circulating tumor cells (CTCs) carry intact tumor molecular information, making them invaluable for personalized cancer monitoring. However, conventional capture methods, relying on passive diffusion, suffer from low efficiency due to insufficient collision frequency, severely limiting clinical utility. Herein, a magnetic micromotor‐functionalized DNA‐array hunter (MMDA hunter) is developed by integrating enzyme‐propelled micromotors, magnetic nanoparticles, and nucleic acid aptamers into distinct functional partitions of a DNA tile self‐assembly structure. This design ensured independent and compatible running of autonomous propulsion, targeted recognition, and magnetic enrichment, enabling efficient capture and subsequent identification of CTCs in clinical blood samples. The autonomous motion of the MMDA hunter is powered by O 2 bubbles generated through the dual enzymatic cascade reactions of glucose oxidase and catalase under physiological glucose conditions. Compared to static Fe 3 O 4 arrays (without micromotors), the MMDA hunter shows more than 2‐fold improvement in capture efficiency. Meanwhile, it achieved superb precision, simple operation, rapid response, high biocompatibility, excellent stability, and superior specificity for CTC enrichment. This method provides a reliable tool for tumor diagnosis in multiple clinical application scenarios, even in primary medical care, simultaneously offering a clever solution for the bottleneck of functional‐module interference in multifunctional nanomaterials.