DNA Origami For Cancer Therapy

When most people hear the term DNA which stands for deoxyribose nucleic acid, they think of genetic information, the blueprint for life as we know it. However, beyond its biological role, DNA is fundamentally a polymer with predictable chemical properties and structures that can be engineered and manipulated. Well scientists have done exactly that through the use of DNA outside of its context within genes to create DNA origami, symmetrical DNA patterns that can be constructed by repeatedly folding a long strand of natural DNA and fixing it with the short strand which allow it to form the intended shapes (Liu et al. 2021). These specific structures are created and held together by the complementary base pairing within the different composed nucleotides. The actual creation of DNA origami consists of four steps. In the first step the DNA double helix skeleton chains are arranged in parallel, and the overall outline is similar to the final origami structure. Then a crossover structure is designed, a large number of “staple” chains are added, and the self-assembly of the longer DNA strand and the staple chains are completed under annealing treatment in a specific salt (Zhang et al. 2023).

The resultant geometries from the process described above can be extremely specific and due to this customizability that DNA origami has it can be applied for a wide variety of applications by constructing complex two or three dimensional DNA nanostructures which can serve as effective nanomaterials or molecules (Liu et al. 2021). Of particular note is its applications for cell drug delivery and even more specifically antitumour drug delivery(Zhang et al. 2023; Jafari et al. 2025). This is because they have lower biotoxicity, increased stability, and superior adaptability, and because they can precisely control the location of drug-delivery molecules making them an excellent choice for transporting anti-tumour agents (Liu et al. 2021; Zhang et al. 2023). 

They typically do so through the encapsulation of the drug of choice by the DNA origami structure followed by the release of the drug when a cancer cell is detected by the origami structure (Zhang, Xue, and Yang 2024; Udomprasert and Kangsamaksin 2017). They are able to carry out these actions because DNA can interact with a variety of functional molecules through changes in shape and size, covalent bonding, nucleic acid base pairing, biotin-avidin reaction, intercalation, aptamer-ligand reaction, and DNA-protein reactions (Liu et al. 2021). Their particular strength over current methods lies in the fact that many chemotherapeutics encounter high levels of systemic toxicity due to their non-specific action and issues during delivery to tumours, and although many materials have been explored to improve delivery efficiency most have severe drawbacks (Zhang et al. 2014). These drawbacks include limited biocompatibility and inability to engineer spatially addressable surfaces that can be utilized for multifunctional activity. However, DNA origami has been shown to possess superior tumour passive targeting and long-lasting properties within the tumour region (Zhang et al. 2014). 

Outside of just the delivery the high molecular customizability as mentioned earlier allows for one DNA origami to have multiple applications through actions such as the simultaneous loading of diverse therapeutic agents, adjuvants (substances which enhance the body’s immune response to antigens), or imaging molecules. Despite all these benefits DNA origami can face structural instability under acidic conditions and can be susceptible to enzymatic degradation by nucleases. However, these issues have already been addressed through the development of protective surface coatings, such as peptides (Jafari et al. 2025).

Although DNA origami is still in relatively early stages as a programmable biopolymer capable of forming precise and functional nanostructures with high customizability, biocompatibility, and spatial accuracy it is an extremely promising advancement in targeted cancer therapy.

References

Jafari, Murtaza, Shaiyar Shahryar, Sohameh Mohebbi, et al. 2025. “DNA Nanostructures as Promising Anticancer Agents: A Review.” Cancer Treatment and Research Communications 45 (October): 101029. https://doi.org/10.1016/j.ctarc.2025.101029

Liu, Wei, Huaichuan Duan, Derong Zhang, et al. 2021. “Concepts and Application of DNA Origami and DNA Self-Assembly: A Systematic Review.” Applied Bionics and Biomechanics 2021 (November): 1–15. https://doi.org/10.1155/2021/9112407

Udomprasert, Anuttara, and Thaned Kangsamaksin. 2017. “DNA Origami Applications in Cancer Therapy.” Cancer Science 108 (8): 1535–43. https://doi.org/10.1111/cas.13290

Zhang, Qian, Qiao Jiang, Na Li, et al. 2014. “DNA Origami as an in Vivo Drug Delivery Vehicle for Cancer Therapy.” ACS Nano 8 (7): 6633–43. https://doi.org/10.1021/nn502058j

Zhang, Rui, Tailing Xue, and Dayong Yang. 2024. “BP Neural Network Model for Material Distribution Prediction Based on Variable Amplitude Anti-Blocking Screening DEM Simulations.” Nano Research 18 (7): 94907178–78. https://doi.org/10.26599/nr.2025.94907178

Zhang, Yiming, Xinchen Tian, Z.G. Wang, et al. 2023. “Advanced Applications of DNA Nanostructures Dominated by DNA Origami in Antitumor Drug Delivery.” Frontiers in Molecular Biosciences 10 (August). https://doi.org/10.3389/fmolb.2023.1239952