Structured aptamers are nucleic acid systems produced using DNA nano self-assembly technology and can be constructed in a programmable manner. These aptamers are widely used in biomedical fields because of their low biological toxicity, weak immunogenicity, good cytocompatibility and biocompatibility, stability, and facile modification ability. Additionally, structured aptamers achieve nano precision in spatial configuration and can be directly internalized into targets without the assistance of transfection reagents. They exhibit higher stability, rigidity, and binding efficiency than aptamers alone. Therefore, structured aptamers have been universally applied in the tumor-targeting field and have emerged as a current research hotspot. Here, we introduce the assembly principle, assembly methods, and characterization methods of structured aptamers. Moreover, the application status of structured aptamers for tumor detection and targeted therapy is summarized to provide new research directions for early diagnosis and drug research in the field of oncology.

Nucleolin protein expression is higher on the ovarian cancer cell surface. AS1411, a DNA aptamer, can bind with nucleolin protein specifically. In this study, we developed HA and ST DNA tiles to assemble six AS1411 aptamers to deliver doxorubicin. In addition, to superior serum stability and drug loading, HA-6AS and ST-6AS outperformed TDN-AS in cellular uptake. HA-6AS and ST-6AS exhibited satisfactory targeted cytotoxicity and achieved resounding lysosomal escape. Moreover, when injected into nude mice subcutaneous xenograft models, HA-6AS reached the peak in tumor more quickly than ST-6AS, and better expressed the active targeting ability of AS1411. Our study suggests that designing appropriate DNA tiles to assemble different aptamers to deliver different chemotherapeutic drugs is a promising treatment for ovarian cancer.