DNA nanotechnology in oligonucleotide drug delivery systems: Prospects for Bio-nanorobots in cancer treatment

DNA-based nanomaterials have demonstrated significant potential in various applications due to their unique properties, including DNA's diverse molecular interactions, programmability, and versatility with biological modules. Meanwhile, the DNA origami platforms have shown promise in the creation of drug carriers. This technique has paved the way for the production of nanomachines with outstanding performance. Moreover, DNA's encoding capability and its massive parallelism help us to manipulate it for DNA computation. The DNA nanotechnology method holds potential, particularly for oligonucleotide therapeutics that enable precision medicine for cancers. In this review, we explore the potential of DNA nanotechnology in this context, focusing on the DNA origami method and its production challenges, and proposing streamlined methods to enhance scalability and efficiency by enzymatic tools in life-like artificial systems. We then delve into studies demonstrating the application of DNA nanotechnology in delivering oligonucleotide drugs for tumor targeting. Following this, we assess DNA-based dynamic nanodevices that can be activated through molecular binding, environmental stimuli, and external field manipulation. Subsequently, we investigate the significance of DNA computation in the production of logic gates, DNA circuits, data storage, and machine learning, along with its role in drug delivery approaches. By systematically classifying DNA robots according to their fundamental operating mechanisms, Machinery DNA Robots (MDNARs) and Computational DNA Robots (CDNARs), we pave the way for next-generation ’Bio-nanorobots.’ These advanced systems can integrate DNA computation with dynamic DNA machinery to enable precision cancer therapeutics through intelligent molecular-scale operations.