DNA origami-based drug delivery and cell manipulation: toward intelligent nanomedicine

DNA origami has emerged as a versatile platform for constructing nanoscale architectures with precise shape programmability, molecular-level addressability, and dynamic structural reconfigurability. Since its introduction, DNA origami has evolved from a structural design method into a functional nanosystem capable of integrating molecular recognition, logic-gated operations, and mechanical motion, enabling a wide range of biomedical applications. This review outlines recent advances in DNA origami-based drug delivery and the regulation of cellular functions and cell fate. Strategic control over size, shape, and mechanical properties is discussed in the context of cellular uptake, intracellular behavior, and the efficient delivery of small-molecule drugs and nucleic acid therapeutics. Recent progress in dynamic DNA origami nanodevices and nanorobots that respond to molecular, chemical, or physical cues is highlighted, including systems that enable spatiotemporally controlled payload release and the nanoscale organization of membrane receptors to modulate cellular signaling. In addition, key stabilization strategies required for in vivo applications, such as covalent linking of constituent DNA strands and surface-coating methods, are summarized. Finally, future challenges and perspectives are discussed, emphasizing the growing role of chemical biology in endowing DNA origami with sensing, decision-making, and adaptive functions for intelligent nanomedicine.