A battery-free nanofluidic intracellular delivery patch for internal organs

Dedong Yin^#^{1

2

3}, Pan Wang^#², Yongcun Hao^#^{4

5}, Wei Yue^#⁶, Xinran Jiang^#¹, Kuanming Yao⁷, Yuqiong Wang¹, Xinxin Hang¹, Ao Xiao¹, Jingkun Zhou⁷, Long Lin¹, Zhoulyu Rao⁸, Han Wu¹, Feng Liu¹, Zaizai Dong¹, Meng Wu⁹, Chenjie Xu⁷, Jiandong Huang^{10

11}, Honglong Chang⁴, Yubo Fan¹, Xinge Yu^{12

13

14}, Cunjiang Yu^{15

16}, Lingqian Chang¹⁷, Mo Li^{18

19

20}

Affiliations

¹ Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
² State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
³ Institute of Science and Technology of National Health Commission, Beijing, China.
⁴ MOE Key Laboratory of Micro and Nano Systems for Aerospace, School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an, China.
⁵ Ningbo Institute of Northwestern Polytechnical University, Ningbo, China.
⁶ Interdisciplinary Eye Research Institute (EYE-X Institute), Bengbu Medical University, Bengbu, China.
⁷ Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
⁸ Materials Research Laboratory, University of Illinois Urbana-Champaign, Urbana, IL, USA.
⁹ Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
¹⁰ School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
¹¹ Materials Innovation Institute for Life Sciences and Energy (MILES), HKU-SIRI, Shenzhen, China.
¹² Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China. xingeyu@cityu.edu.hk.
¹³ Institute of Digital Medicine, City University of Hong Kong, Hong Kong, China. xingeyu@cityu.edu.hk.
¹⁴ Hong Kong Institute for Clean Energy, City University of Hong Kong, Hong Kong, China. xingeyu@cityu.edu.hk.
¹⁵ Materials Research Laboratory, University of Illinois Urbana-Champaign, Urbana, IL, USA. cunjiang@illinois.edu.
¹⁶ Department of Electrical and Computer Engineering, Department of Materials Science and Engineering, Department of Bioengineering, Department of Mechanical Science and Engineering, Nick Holonyak Micro and Nanotechnology Laboratory, Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, USA. cunjiang@illinois.edu.
¹⁷ Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China. lingqianchang@buaa.edu.cn.
¹⁸ State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China. limo@hsc.pku.edu.cn.
¹⁹ National Clinical Research Center for Obstetrics and Gynecology, Third Hospital, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. limo@hsc.pku.edu.cn.
²⁰ Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China. limo@hsc.pku.edu.cn.

^# Contributed equally.

PMID: 40307560
DOI: 10.1038/s41586-025-08943-x

A battery-free nanofluidic intracellular delivery patch for internal organs

Dedong Yin et al. Nature. 2025 Jun.

. 2025 Jun;642(8069):1051-1061.

doi: 10.1038/s41586-025-08943-x. Epub 2025 Apr 30.

Authors

Affiliations

¹ Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
² State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
³ Institute of Science and Technology of National Health Commission, Beijing, China.
⁴ MOE Key Laboratory of Micro and Nano Systems for Aerospace, School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an, China.
⁵ Ningbo Institute of Northwestern Polytechnical University, Ningbo, China.
⁶ Interdisciplinary Eye Research Institute (EYE-X Institute), Bengbu Medical University, Bengbu, China.
⁷ Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
⁸ Materials Research Laboratory, University of Illinois Urbana-Champaign, Urbana, IL, USA.
⁹ Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
¹⁰ School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
¹¹ Materials Innovation Institute for Life Sciences and Energy (MILES), HKU-SIRI, Shenzhen, China.
¹² Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China. xingeyu@cityu.edu.hk.
¹³ Institute of Digital Medicine, City University of Hong Kong, Hong Kong, China. xingeyu@cityu.edu.hk.
¹⁴ Hong Kong Institute for Clean Energy, City University of Hong Kong, Hong Kong, China. xingeyu@cityu.edu.hk.
¹⁵ Materials Research Laboratory, University of Illinois Urbana-Champaign, Urbana, IL, USA. cunjiang@illinois.edu.
¹⁶ Department of Electrical and Computer Engineering, Department of Materials Science and Engineering, Department of Bioengineering, Department of Mechanical Science and Engineering, Nick Holonyak Micro and Nanotechnology Laboratory, Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, USA. cunjiang@illinois.edu.
¹⁷ Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China. lingqianchang@buaa.edu.cn.
¹⁸ State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China. limo@hsc.pku.edu.cn.
¹⁹ National Clinical Research Center for Obstetrics and Gynecology, Third Hospital, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. limo@hsc.pku.edu.cn.
²⁰ Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China. limo@hsc.pku.edu.cn.

^# Contributed equally.

PMID: 40307560
DOI: 10.1038/s41586-025-08943-x

Abstract

The targeted delivery of therapeutics to internal organs to, for example, promote healing or apoptosis holds promise in the treatment of numerous diseases^1-4. Currently, the prevailing delivery modality relies on the circulation; however, this modality has substantial efficiency, safety and/or controllability limitations^5-9. 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.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

1. Gillmore, J. D. et al. CRISPR–Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021). - PubMed - DOI
1. Mendell, J. R. et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 377, 1713–1722 (2017). - PubMed - DOI
1. Pasi, K. J. et al. Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A. N. Engl. J. Med. 382, 29–40 (2020). - PubMed - DOI
1. Sahin, U. et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature 585, 107–112 (2020). - PubMed - DOI
1. Kulkarni, J. A. et al. The current landscape of nucleic acid therapeutics. Nat. Nanotechnol. 16, 630–643 (2021). - PubMed - DOI

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A battery-free nanofluidic intracellular delivery patch for internal organs

Affiliations

A battery-free nanofluidic intracellular delivery patch for internal organs

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

LinkOut - more resources

Full Text Sources

Medical