DNA nanostructures, composed of DNA, serve as both structural and functional elements, capable of self-assembling into complex 3D shapes through Watson-Crick base pairing. These structures offer high stability, thermodynamic control, and the ability to be modified for various applications, including drug delivery. DNA nanostructures, such as DNA origami, tetrahedrons, nanoflowers, and nanocentipedes, can traverse cell membranes to deliver cargo to the nucleus. Aptamers, which are highly selective and low immunogenic, are used for targeted delivery due to their ability to bind specific targets. This review discusses recent advancements in the formation and modification of aptamer-modified DNA nanostructures for drug delivery, emphasizing their stability, biocompatibility, and ability to target specific cells. DNA nanostructures are designed with modular, branched building blocks to create intricate, higher-order structures. Their noncovalent and reversible nature allows for precise control over self-assembly, enabling the fabrication of nanostructures according to predefined specifications. These structures can be functionalized with ligands, such as aptamers, to enhance their targeting capabilities. DNA nanostructures have been shown to resist degradation under physiological conditions, with factors such as magnesium ion concentration, pH, and the presence of nucleases influencing their stability. Strategies to enhance nuclease resistance include coating, modification, and the use of inhibitors. DNA nanostructures have been used for targeted drug delivery, with DNA origami and tetrahedrons showing particular promise. These structures can be modified with aptamers to target specific receptors on cancer cells, facilitating drug release. DNA origami has been used to deliver doxorubicin (DOX) and other therapeutic agents, with studies showing improved efficacy and reduced toxicity. DNA tetrahedrons have also been used for drug delivery, with their high stability and ability to be modified for various applications. These structures can be used to deliver siRNA and other therapeutic agents, demonstrating their potential in gene therapy and cancer treatment. The use of DNA nanostructures in drug delivery has been shown to enhance the targeting and delivery of drugs to specific cells, with studies demonstrating improved efficacy and reduced side effects. These structures can be functionalized with aptamers to target specific receptors, allowing for precise drug delivery. The stability of DNA nanostructures under physiological conditions is crucial for their effectiveness, with factors such as magnesium ion concentration, pH, and the presence of nucleases influencing their stability. Strategies to enhance nuclease resistance include coating, modification, and the use of inhibitors. Overall, DNA nanostructures offer a promising platform for targeted drug delivery, with their unique properties making them suitable for various applications in medicine.DNA nanostructures, composed of DNA, serve as both structural and functional elements, capable of self-assembling into complex 3D shapes through Watson-Crick base pairing. These structures offer high stability, thermodynamic control, and the ability to be modified for various applications, including drug delivery. DNA nanostructures, such as DNA origami, tetrahedrons, nanoflowers, and nanocentipedes, can traverse cell membranes to deliver cargo to the nucleus. Aptamers, which are highly selective and low immunogenic, are used for targeted delivery due to their ability to bind specific targets. This review discusses recent advancements in the formation and modification of aptamer-modified DNA nanostructures for drug delivery, emphasizing their stability, biocompatibility, and ability to target specific cells. DNA nanostructures are designed with modular, branched building blocks to create intricate, higher-order structures. Their noncovalent and reversible nature allows for precise control over self-assembly, enabling the fabrication of nanostructures according to predefined specifications. These structures can be functionalized with ligands, such as aptamers, to enhance their targeting capabilities. DNA nanostructures have been shown to resist degradation under physiological conditions, with factors such as magnesium ion concentration, pH, and the presence of nucleases influencing their stability. Strategies to enhance nuclease resistance include coating, modification, and the use of inhibitors. DNA nanostructures have been used for targeted drug delivery, with DNA origami and tetrahedrons showing particular promise. These structures can be modified with aptamers to target specific receptors on cancer cells, facilitating drug release. DNA origami has been used to deliver doxorubicin (DOX) and other therapeutic agents, with studies showing improved efficacy and reduced toxicity. DNA tetrahedrons have also been used for drug delivery, with their high stability and ability to be modified for various applications. These structures can be used to deliver siRNA and other therapeutic agents, demonstrating their potential in gene therapy and cancer treatment. The use of DNA nanostructures in drug delivery has been shown to enhance the targeting and delivery of drugs to specific cells, with studies demonstrating improved efficacy and reduced side effects. These structures can be functionalized with aptamers to target specific receptors, allowing for precise drug delivery. The stability of DNA nanostructures under physiological conditions is crucial for their effectiveness, with factors such as magnesium ion concentration, pH, and the presence of nucleases influencing their stability. Strategies to enhance nuclease resistance include coating, modification, and the use of inhibitors. Overall, DNA nanostructures offer a promising platform for targeted drug delivery, with their unique properties making them suitable for various applications in medicine.