A battery-free nanofluidic intracellular delivery patch for internal organs

Dedong Yin, Pan Wang, Yongcun Hao, Wei Yue, Xinran Jiang, Kuanming Yao, Yuqiong Wang, Xinxin Hang, Ao Xiao, Jingkun Zhou, Long Lin, Zhoulyu Rao, Han Wu, Feng Liu, Zaizai Dong, Meng Wu, Chenjie Xu, Jiandong Huang, Honglong Chang, Yubo Fan, Xinge Yu (), Cunjiang Yu (), Lingqian Chang () and Mo Li ()
Additional contact information
Dedong Yin: Beihang University
Pan Wang: Peking University Third Hospital
Yongcun Hao: Northwestern Polytechnical University
Wei Yue: Bengbu Medical University
Xinran Jiang: Beihang University
Kuanming Yao: City University of Hong Kong
Yuqiong Wang: Beihang University
Xinxin Hang: Beihang University
Ao Xiao: Beihang University
Jingkun Zhou: City University of Hong Kong
Long Lin: Beihang University
Zhoulyu Rao: University of Illinois Urbana–Champaign
Han Wu: Beihang University
Feng Liu: Beihang University
Zaizai Dong: Beihang University
Meng Wu: Tsinghua University
Chenjie Xu: City University of Hong Kong
Jiandong Huang: The University of Hong Kong
Honglong Chang: Northwestern Polytechnical University
Yubo Fan: Beihang University
Xinge Yu: City University of Hong Kong
Cunjiang Yu: University of Illinois Urbana–Champaign
Lingqian Chang: Beihang University
Mo Li: Peking University Third Hospital

Nature, 2025, vol. 642, issue 8069, 1051-1061

Abstract: Abstract The targeted delivery of therapeutics to internal organs to, for example, promote healing or apoptosis holds promise in the treatment of numerous diseases1–4. Currently, the prevailing delivery modality relies on the circulation; however, this modality has substantial efficiency, safety and/or controllability limitations5–9. 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 105 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.

Date: 2025
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DOI: 10.1038/s41586-025-08943-x

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