Advances in programmable DNA nanostructures enabling stimuli-responsive drug delivery and multimodal biosensing
Yao Hong, Wenyue Ma, Meixia Wang, Hong-Hui Wang
Abstract
polyethylene glycol (PEG) functionalization, and multi-ligand targeting capabilities against cancer-specific biomarkers. In addition to therapeutic uses, these nanostructures also enable highly sensitive detection of circulating tumor DNA and exosomes using fluorescence resonance energy transfer (FRET) probes, electrochemiluminescence amplification circuits, SERS substrates, and cell variable region sensing technology. They also allow for real-time monitoring of dynamic intercellular interactions, overcoming the constraints of traditional sensing methods. This review systematically elaborates on the structural characteristics of DNA assemblies and summarizes the innovative applications of these nanostructures in multimodal detection, offering a more comprehensive perspective for early cancer diagnosis and precision treatment. Despite promising preclinical results, key translational challenges persist, including scalable manufacturing bottlenecks, immune compatibility optimization, and rigorous assessment of long-term nanotoxicity. Future integration with artificial intelligence-driven design tools may catalyze the development of next-generation theranostic nanodevices, ultimately bridging the gap between synthetic biology and clinical oncology.