寡核苷酸给药系统中的DNA纳米技术：生物纳米机器人在癌症治疗中的前景。

Abdollahzadeh Haniyeh, Peeples Tonya L, Shahcheraghi Mohammad

Waltemeyer Department of Chemical Engineering, Pennsylvania State University, University Park, PA, USA.

Pennsylvania State University, University Park, PA, USA.

Adv Drug Deliv Rev. 2025 Aug 11;225:115673. doi: 10.1016/j.addr.2025.115673.

DNA-based nanomaterials have demonstrated significant potential in various applications due to their unique properties, including DNA's diverse molecular interactions, programmability, and versatility with biological modules. Meanwhile, the DNA origami platforms have shown promise in the creation of drug carriers. This technique has paved the way for the production of nanomachines with outstanding performance. Moreover, DNA's encoding capability and its massive parallelism help us to manipulate it for DNA computation. The DNA nanotechnology method holds potential, particularly for oligonucleotide therapeutics that enable precision medicine for cancers. In this review, we explore the potential of DNA nanotechnology in this context, focusing on the DNA origami method and its production challenges, and proposing streamlined methods to enhance scalability and efficiency by enzymatic tools in life-like artificial systems. We then delve into studies demonstrating the application of DNA nanotechnology in delivering oligonucleotide drugs for tumor targeting. Following this, we assess DNA-based dynamic nanodevices that can be activated through molecular binding, environmental stimuli, and external field manipulation. Subsequently, we investigate the significance of DNA computation in the production of logic gates, DNA circuits, data storage, and machine learning, along with its role in drug delivery approaches. By systematically classifying DNA robots according to their fundamental operating mechanisms, Machinery DNA Robots (MDNARs) and Computational DNA Robots (CDNARs), we pave the way for next-generation 'Bio-nanorobots.' These advanced systems can integrate DNA computation with dynamic DNA machinery to enable precision cancer therapeutics through intelligent molecular-scale operations.

基于DNA的纳米材料因其独特的性质，在各种应用中展现出了巨大的潜力，这些性质包括DNA多样的分子相互作用、可编程性以及与生物模块的通用性。同时，DNA折纸平台在药物载体的构建方面显示出了前景。这项技术为生产具有卓越性能的纳米机器铺平了道路。此外，DNA的编码能力及其大规模并行性有助于我们对其进行操作以实现DNA计算。DNA纳米技术方法具有潜力，特别是对于能够实现癌症精准医疗的寡核苷酸疗法。在本综述中，我们探讨了DNA纳米技术在这一背景下的潜力，重点关注DNA折纸方法及其生产挑战，并提出了通过类生命人工系统中的酶工具来提高可扩展性和效率的简化方法。然后，我们深入研究了证明DNA纳米技术在递送用于肿瘤靶向的寡核苷酸药物方面的应用的研究。在此之后，我们评估了可通过分子结合、环境刺激和外部场操纵激活的基于DNA的动态纳米器件。随后，我们研究了DNA计算在逻辑门、DNA电路、数据存储和机器学习生产中的重要性，以及它在药物递送方法中的作用。通过根据其基本操作机制对DNA机器人进行系统分类，即机械DNA机器人（MDNARs）和计算DNA机器人（CDNARs），我们为下一代“生物纳米机器人”铺平了道路。这些先进系统可以将DNA计算与动态DNA机械相结合，通过智能分子尺度操作实现精准癌症治疗。