Yin Dedong, Wang Pan, Hao Yongcun, Yue Wei, Jiang Xinran, Yao Kuanming, Wang Yuqiong, Hang Xinxin, Xiao Ao, Zhou Jingkun, Lin Long, Rao Zhoulyu, Wu Han, Liu Feng, Dong Zaizai, Wu Meng, Xu Chenjie, Huang Jiandong, Chang Honglong, Fan Yubo, Yu Xinge, Yu Cunjiang, Chang Lingqian, Li Mo
Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
Nature. 2025 Apr 30. doi: 10.1038/s41586-025-08943-x.
The targeted delivery of therapeutics to internal organs to, for example, promote healing or apoptosis holds promise in the treatment of numerous diseases. Currently, the prevailing delivery modality relies on the circulation; however, this modality has substantial efficiency, safety and/or controllability limitations. Here we report a battery-free, chipless, soft nanofluidic intracellular delivery (NanoFLUID) patch that provides enhanced and customized delivery of payloads in targeted internal organs. The chipless architecture and the flexible nature of thin functional layers facilitate integration with internal organs. The nanopore-microchannel-microelectrode structure enables safe, efficient and precise electroperforation of the cell membrane, which in turn accelerates intracellular payload transport by approximately 10 times compared with conventional diffusion methods while operating under relatively low-amplitude pulses (20 V). Through evaluations of the NanoFLUID patch in multiple in vivo scenarios, including treatment of breast tumours and acute injury in the liver and modelling tumour development, we validated its efficiency, safety and controllability for organ-targeted delivery. NanoFLUID-mediated in vivo transfection of a gene library also enabled efficient screening of essential drivers of breast cancer metastasis in the lung and liver. Through this approach, DUS2 was identified as a lung-specific metastasis driver. Thus, NanoFLUID represents an innovative bioelectronic platform for the targeted delivery of payloads to internal organs to treat various diseases and to uncover new insights in biology.
将治疗药物靶向递送至内部器官，例如促进愈合或诱导细胞凋亡，在多种疾病的治疗中具有广阔前景。目前，主流的递送方式依赖于血液循环；然而，这种方式在效率、安全性和/或可控性方面存在显著局限性。在此，我们报告了一种无电池、无芯片的柔性纳米流体细胞内递送（NanoFLUID）贴片，它能够在目标内部器官中实现增强的、定制化的药物递送。无芯片架构以及薄功能层的柔性特性便于与内部器官集成。纳米孔-微通道-微电极结构能够对细胞膜进行安全、高效且精确的电穿孔，与传统扩散方法相比，在相对低幅度脉冲（20 V）下操作时，这反过来能使细胞内药物运输加速约10倍。通过在多种体内场景中对NanoFLUID贴片进行评估，包括治疗乳腺肿瘤、肝脏急性损伤以及模拟肿瘤发展，我们验证了其在器官靶向递送方面的效率、安全性和可控性。NanoFLUID介导的体内基因文库转染还能够高效筛选肺和肝脏中乳腺癌转移的关键驱动因素。通过这种方法，DUS2被确定为肺特异性转移驱动因素。因此，NanoFLUID代表了一种创新的生物电子平台，用于将药物靶向递送至内部器官，以治疗各种疾病并揭示生物学中的新见解。
