This review discusses the assembly methods of nucleic acid-functionalized metal nanoparticles (N-MNPs), metal nanoparticles supramolecular assembly strategies, and their representative applications in biological diagnosis and therapy.

DNA nanotechnology offers an unprecedented level of structural programmability for organizing metallic nanoparticles into precisely defined architectures, providing a powerful platform for plasmonic biosensing. In particular, gold and silver nanoparticles assembled on DNA nanostructures enable nanometer-scale control over interparticle distance, orientation, and spatial symmetry, which directly govern collective plasmonic behaviors and optical signal transduction. This review summarizes recent advances in DNA nanostructure-mediated assembly of metal nanoparticles, with an emphasis on design principles and assembly strategies that enable static and dynamic control of nanoparticle organization. Representative examples are discussed to illustrate how well-defined plasmonic assemblies give rise to tunable optical responses, including localized surface plasmon resonance modulation, chiroptical signals, fluorescence enhancement or quenching, and surface-enhanced Raman scattering. The role of structural programmability and stimulus-responsive reconfiguration in translating molecular recognition events into amplified optical outputs is highlighted in the context of biosensing. Finally, current challenges and future perspectives are outlined, focusing on structural robustness, signal reproducibility, and integration toward practical and multiplexed biosensing platforms.

Nanozymes, exemplified by metal nanoparticles, have shown promise in the fields of biological diagnostics and therapeutics. However, their practical application is often hindered by aggregation or deactivation in complex biological systems. Here, we develop a DNA-engineered nanozyme coating to preserve the peroxidase-like catalytic activity of platinum nanoparticles in complex biological environments. We employed thiol-modified single-stranded DNA to coat the platinum nanoparticles through metal–sulfur interaction. We found that the negatively charged DNA coating prevents the aggregation of platinum nanoparticles in high-salt environments. Moreover, the DNA coating functions as a molecular sieve, inhibiting non-specific protein adsorption while preserving substrate access to the catalytic interface, thus sustaining high peroxidase-like catalytic activity in serum. As a proof of concept, we demonstrate miRNA detection in serum samples with a detection limit of 1 fM. This approach offers a versatile strategy for molecular diagnostics of nanozymes in complex biological environments.

DNA origami technology has shown potential across various applications, including the construction of molecular machines. Among these, mimicking the complex structural transitions of natural biomolecules in physiological environments remains a long-standing pursuit. Here, inspired by intrinsically disordered proteins, we propose a strategy for inducing disorder-to-order transitions in DNA origami structures at room temperature using alternative component subsets. In a triangular DNA origami model, we define three subsets of its constitutional DNA staples based on their spatial distributions along the scaffold. Atomic force microscopy and molecular dynamics simulations show that the individual subsets result in metastable assemblies with disordered morphologies and elevated free-energy fluctuations compared with those generated by the complete set of staples. Notably, after the addition of the remaining staples, the irregular structures transform into ordered triangular architectures within 2 h at room temperature, achieving yields of up to ∼60%. These findings suggest that these controlled folding pathways in DNA origami can robustly converge on the global energy minimum at room temperature, thereby providing a promising alternative strategy for engineering biomimetic DNA molecular machines.

Nucleic acid nanotechnology-based artificial transcriptional components (aTCs) can be integrated into synthetic transcriptional circuits to recognize external signals, process information, and execute decision-based functions.

A dynamic six‑helix DNA nanomachine enables reversible conformational switching across a broad physiological pH window (5–9), establishing a quantitative performance benchmark for designing dynamic DNA devices in complex biological environments.