DNA Nanotechnologyfor Effective Cancer Immunotherapy

Abstract Cancer immunotherapy has transformed oncological treatment by harnessing the immune system to target tumors. However, challenges such as drug resistance, poor immunogenicity, and inefficient antigen delivery limit its full potential. DNA nanotechnology offers a transformative solution through the development of programmable, biocompatible nanostructures capable of precise antigen presentation, codelivery of immunostimulatory agents, and modulation of the tumor microenvironment. DNA nanostructures, including origami, tetrahedra, and virus-like particles, enable multivalent display of tumor antigens, incorporation of adjuvants like CpG oligodeoxynucleotides, and encapsulation of therapeutic RNAs such as mRNA and siRNA. These features enhance antigen presentation, improve endosomal escape, and stimulate robust innate and adaptive immune responses. Moreover, bispecific DNA nanoconstructs can bridge immune effector cells with tumor cells, simulating immune synapses and enhancing cytotoxicity. The modularity and precision of DNA scaffolds also support patient-specific vaccine development, particularly when integrated with genomic sequencing and CRISPR-based neoantigen discovery. Virus-inspired DNA nanostructures further mimic native viral immunogenicity while allowing safer, customizable antigen loading. Future efforts should focus on overcoming translational barriers, including scalable manufacturing, in vivo stability, and regulatory standardization. With continued advances in structural design, ligand functionalization, and immune engineering, DNA nanotechnology holds the potential to reshape cancer immunotherapy. It paves the way for highly targeted, personalized, and effective treatments that outperform current clinical approaches in specificity, efficacy, and safety.