Farooq Muhammad Umar, Lawrie Charles H, Deng Nan-Nan
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
Adv Mater. 2025 Jul 11:e2508047. doi: 10.1002/adma.202508047.
Despite decades of research, cancer remains a growing global health challenge. Nanomaterials-based therapeutics have shown promise, but their clinical applications are often limited by poor selectivity and undesirable side effects. Recently, deoxyribonucleic acid (DNA) based nanomachines have gained attention as intelligent drug carriers due to their ability to precisely target specific organelles. By leveraging rationally designed DNA nanomachines, it is possible to directly attack subcellular structures or deliver therapeutic agents to precise locations, triggering organelle-mediated cell death. This innovative approach offers several advantages, including enhanced efficacy, lower dosages, minimized off-target effects, reduced multidrug resistance, and improved therapeutic durability. This review explores the history and advancements of organelle-targeting strategies, providing new insights into targeting the nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosomes using DNA nanomachines. The review also discusses the structures, design principles, and therapeutic mechanisms of these nanomachines, along with the integration of artificial intelligence-driven self-driving laboratories to enhance research growth, efficiency, and competitiveness. Finally, the current challenges, opportunities, and future directions in this evolving field are addressed, offering a roadmap for solving the intricate maze of organelle-targeted cancer therapies.
尽管经过了数十年的研究，癌症仍然是一个日益严峻的全球健康挑战。基于纳米材料的疗法已显示出前景，但其临床应用往往受到选择性差和不良副作用的限制。最近，基于脱氧核糖核酸（DNA）的纳米机器作为智能药物载体受到关注，因为它们能够精确靶向特定细胞器。通过利用合理设计的DNA纳米机器，可以直接攻击亚细胞结构或将治疗剂递送至精确位置，引发细胞器介导的细胞死亡。这种创新方法具有多种优势，包括提高疗效、降低剂量、将脱靶效应降至最低、减少多药耐药性以及提高治疗持久性。本综述探讨了细胞器靶向策略的历史和进展，为使用DNA纳米机器靶向细胞核、线粒体、内质网、高尔基体和溶酶体提供了新的见解。综述还讨论了这些纳米机器的结构、设计原则和治疗机制，以及人工智能驱动的自动驾驶实验室的整合，以促进研究发展、提高效率和增强竞争力。最后，阐述了这一不断发展的领域当前面临的挑战、机遇和未来方向，为解决细胞器靶向癌症治疗的复杂难题提供了路线图。
