Wang Keqing, Zhu Wenjing, Li Xin, Ling Guixia, Zhang Peng
Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Acta Biomater. 2025 Sep 17. doi: 10.1016/j.actbio.2025.09.020.
DNA walkers play a strategic role in precision medicine for applications such as single-cell analysis and tumor microenvironment modulation, yet face bottlenecks in stability, efficiency, and physiological adaptability. A DNA walker primarily comprises a walking strand, track, and driving force. DNAzyme-driven walkers achieve autonomous movement via enzymatic catalysis, eliminating reliance on external energy. The AuNP-DNAzyme synergy overcomes bottlenecks via surface plasmon resonance, thiol chemistry, and nanoconfinement for signal enhancement, dense DNA modification, and enzyme stabilization. Compared to DNA fuel or protease-powered walkers, this strategy enhances processivity and stability while reducing costs. This review is structured around "structure-performance-application": it first outlines the components of DNA walkers and the structural roles of AuNPs, then discusses performance optimization through 3D tracks and DNAzyme tuning, and finally summarizes applications in molecular imaging and biosensing. Future development trends of DNA walkers have been delved into, and their research prospects have been presented in this article, with a focus on theranostic integration and in vivo dynamic imaging, positioning DNA walkers as intelligent platforms for precision diagnostics and targeted therapy. STATEMENT OF SIGNIFICANCE: This review highlights the transformative potential of DNAzyme-driven DNA walkers, which leverage the autonomous catalytic activity of DNAzymes to achieve unparalleled operational efficiency, stability, cost-effectiveness, and programmability compared to conventional fuel strand- or protease-powered systems. Central to their advancement is the integration of gold nanoparticles (AuNPs), whose exceptional biocompatibility, large surface area, and versatile surface functionalization capabilities enable robust construction and enhanced performance of DNA walker platforms. By systematically outlining the synergy between DNAzyme walkers and AuNPs, this work underscores their groundbreaking applications in biosensing and molecular imaging, offering ultrasensitive detection and precise spatial resolution for biomedical research. Furthermore, the discussion on future trends positions DNA walkers as pivotal tools poised to drive innovation in nanotechnology, diagnostics, and targeted therapeutics, bridging fundamental science with real-world clinical and analytical challenges.
DNA步行器在精准医学中对于单细胞分析和肿瘤微环境调控等应用发挥着重要作用，但在稳定性、效率和生理适应性方面面临瓶颈。DNA步行器主要由行走链、轨道和驱动力组成。基于DNAzyme的步行器通过酶催化实现自主移动，无需依赖外部能量。金纳米颗粒（AuNP）与DNAzyme的协同作用通过表面等离子体共振、硫醇化学和纳米限域效应克服了瓶颈，实现了信号增强、密集DNA修饰和酶稳定化。与基于DNA燃料或蛋白酶驱动的步行器相比，该策略提高了持续合成能力和稳定性，同时降低了成本。本综述围绕“结构-性能-应用”展开：首先概述了DNA步行器的组成部分以及AuNP的结构作用，然后讨论了通过三维轨道和DNAzyme调控进行性能优化，最后总结了在分子成像和生物传感中的应用。本文深入探讨了DNA步行器的未来发展趋势，并展示了其研究前景，重点关注治疗诊断一体化和体内动态成像，将DNA步行器定位为精准诊断和靶向治疗的智能平台。重要性声明：本综述强调了基于DNAzyme的DNA步行器的变革潜力，与传统的燃料链或蛋白酶驱动系统相比，其利用DNAzyme的自主催化活性实现了无与伦比的操作效率、稳定性、成本效益和可编程性。其发展的核心是金纳米颗粒（AuNP）的整合，其卓越的生物相容性、大表面积和多功能表面功能化能力使DNA步行器平台能够实现强大的构建和性能提升。通过系统地概述DNAzyme步行器与AuNP之间的协同作用，本研究强调了它们在生物传感和分子成像中的开创性应用，为生物医学研究提供了超灵敏检测和精确的空间分辨率。此外，对未来趋势的讨论将DNA步行器定位为推动纳米技术、诊断和靶向治疗创新的关键工具，弥合基础科学与现实世界临床及分析挑战之间的差距。
