Gao Di, Xu Ziqi, Li Xiangli, Zhao Yuhan, Min Qianhao, Chen Zixuan, Xu Qin, Tian Ye, Xu Junpeng, Zhu Jun-Jie
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
Collaborative Innovation Center of Biomedical Functional Materials and Key Laboratory of Biofunctional Materials of Jiangsu Province, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China.
Angew Chem Int Ed Engl. 2025 Jun 10;64(24):e202505290. doi: 10.1002/anie.202505290. Epub 2025 Apr 16.
Delivering biomacromolecules to the cytosol remains a formidable challenge, as these molecules are predominantly sequestered within endosomes after endocytosis. The limited efficacy of current delivery systems in promoting reliable endosomal escape underscores the need for innovative strategies. Here, we report a DNA origami nanotubule to construct transmembrane delivery nanodevices with size-selective gating and ATP-responsive channel activation. By integrating unilamellar vesicles as large storage compartments, these nanodevices can encapsulate a wide range of macromolecules, including small interfering RNA, messenger RNA, plasmid DNA, and CRISPR-Cas9 ribonucleoprotein complexes. By bypassing traditional endocytic pathways, the nanotubules enable the delivery of substantial payload quantities directly across the plasma membrane. This approach provides a promising platform for delivering macromolecular therapeutics into the cytosol, advancing gene therapy strategies, and broadening their biomedical applications.
将生物大分子递送至细胞质仍然是一项艰巨的挑战，因为这些分子在胞吞作用后主要被隔离在内体中。当前递送系统在促进可靠的内体逃逸方面效果有限，这凸显了创新策略的必要性。在此，我们报道了一种DNA折纸纳米管，用于构建具有尺寸选择性门控和ATP响应通道激活的跨膜递送纳米装置。通过整合单层囊泡作为大型储存隔室，这些纳米装置可以封装多种大分子，包括小干扰RNA、信使RNA、质粒DNA和CRISPR-Cas9核糖核蛋白复合物。通过绕过传统的内吞途径，纳米管能够直接将大量有效载荷穿过质膜进行递送。这种方法为将大分子治疗剂递送至细胞质、推进基因治疗策略以及拓宽其生物医学应用提供了一个有前景的平台。
