Elblová Petra, Anthi Judita, Liu Minghui, Lunova Mariia, Jirsa Milan, Stephanopoulos Nicholas, Lunov Oleg
FZU - Institute of Physics of the Czech Academy of Sciences, 182 21 Prague, Czech Republic.
Faculty of Mathematics and Physics, Charles University, Ke Karlovu 3, 121 16 Prague 2, Czech Republic.
JACS Au. 2025 Mar 26;5(4):1591-1616. doi: 10.1021/jacsau.5c00117. eCollection 2025 Apr 28.
DNA nanotechnology has revolutionized materials science and biomedicine by enabling precise manipulation of matter at the nanoscale. DNA nanostructures (DNs) in particular represent a promising frontier for targeted therapeutics. Engineered DNs offer unprecedented molecular programmability, biocompatibility, and structural versatility, making them ideal candidates for advanced drug delivery, organelle regulation, and cellular function modulation. This Perspective explores the emerging role of DNs in modulating cellular behavior through organelle-targeted interventions. We highlight current advances in nuclear, mitochondrial, and lysosomal targeting, showcasing applications ranging from gene delivery to cancer therapeutics. For instance, DNs have enabled precision mitochondrial disruption in cancer cells, lysosomal pH modulation to enhance gene silencing, and nuclear delivery of gene-editing templates. While DNs hold immense promise for advancing nanomedicine, outstanding challenges include optimizing biological interactions and addressing safety concerns. This Perspective highlights the current potential of DNs for rational control of targeted organelles, which could lead to novel therapeutic strategies and advancement of precision nanomedicines in the future.
DNA纳米技术通过实现对纳米级物质的精确操控，彻底改变了材料科学和生物医学。特别是DNA纳米结构（DNs）代表了靶向治疗领域一个充满希望的前沿方向。工程化的DNs具有前所未有的分子可编程性、生物相容性和结构多样性，使其成为先进药物递送、细胞器调控和细胞功能调节的理想候选者。这篇综述探讨了DNs在通过细胞器靶向干预调节细胞行为方面的新兴作用。我们强调了目前在细胞核、线粒体和溶酶体靶向方面的进展，展示了从基因递送到癌症治疗等一系列应用。例如，DNs能够精确破坏癌细胞中的线粒体、调节溶酶体pH以增强基因沉默，以及实现基因编辑模板的细胞核递送。虽然DNs在推进纳米医学方面具有巨大潜力，但突出的挑战包括优化生物相互作用和解决安全问题。这篇综述强调了DNs目前在合理控制靶向细胞器方面的潜力，这可能会在未来带来新的治疗策略并推动精准纳米医学的发展。
