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Magnetically driven biohybrid blood hydrogel fibres for personalized intracranial tumour therapy under fluoroscopic tracking

Nature Biomedical Engineering volume 9, pages 1471–1485 (2025)Cite this article

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Abstract

Small materials with pliability and untethered mobility are particularly suitable for minimally invasive medical interventions inside the body. However, the capabilities and applicability of such soft ‘robots’ are restricted by foreign-body responses to them and by the need to get them cleared from the body after the intervention. Here we report the development of biodegradable magnetized biohybrid blood hydrogel fibres that evade immune recognition, and their applicability for targeted intracranial tumour therapy with real-time tracking through X-ray fluoroscopy. The gel fibres can be made of the patient’s own blood mixed with a small amount of magnetic particles and can be produced in about 15 min. We show that the locomotion of intracranially injected gel fibres through cerebrospinal fluid can be remotely controlled under a magnetic field and fluoroscopically tracked, and that a drug encapsulated in the gels can be released on demand under magnetic control, as we show for the delivery of doxorubicin to intracranial tumours in the minipigs. Biodegradable soft actuatable materials that avoid foreign-body responses may aid the development of personalized targeted interventions.

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Fig. 1: Schematic showing the intracranial delivery of the BBHFs under the combined system of magnetic actuation unit and fluoroscopy.
Fig. 2: Fabrication and characterization of BBHFs.
Fig. 3: Mechanical properties of BBHFs.
Fig. 4: Multimode locomotion of BBHFs.
Fig. 5: On-demand drug release by high-strength rotating magnetic field-induced splitting of the robots.
Fig. 6: Intracranial delivery of BBHFs (ex vivo).
Fig. 7: In vivo intracranial tumour therapy in pigs using BBHFs.

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Data availability

The main data supporting the results of this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated during the study are too large to be publicly shared, yet they are available for research purposes from the corresponding authors on reasonable request. Source data are provided with this paper.

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Acknowledgements

We thank C. Zhu from Shenzhen Top Biotechnology Limited Company for their technical support and assistance with the animal experiments. We thank L. Zheng from Shenzhen University for their technical support in materials characterization. We thank the Instrument Analysis Center of Shenzhen University for assistance with the SEM analysis. T.X. discloses support for the publication of this study from the National Key Research and Development Project (2023YFB4705300). B.W. discloses support for the research described in this study from the National Natural Science Foundation of China (52475308), the Shenzhen Science and Technology Innovation Committee Projects (JCYJ20220531103409021) and the Shenzhen Medical Research Fund (SMRF A2303074). J.S. discloses support for the publication of this study from the National Natural Science Foundation of China (52471256) and the Shenzhen Science and Technology Innovation Committee Projects (SGDX20220530111405038, JCYJ20240813115822030). T.X. also discloses support for the publication of this study from the National Natural Science Foundation of China (62022087 and U22A2064), the Shenzhen Science and Technology Innovation Committee Projects (RCJC20231211085926038, RCBS20200714114920190 and JCYJ20220818101611025) and the Guangdong Basic and Applied Basic Research Foundation (2022B1515120010). Z.Y. discloses support for the publication of this study from the Guangdong University Students Science and Technology Innovation Cultivation Special Fund Project (pdjh2023b0450). L.Z. discloses support for the publication of this study from the Hong Kong Research Grants Council (RGC) with Research Impact Fund (R4015-21), the Research Fellow Scheme (RFS2122-4S03), the Strategic Topics Grant (STG1/E-401/23-N) and the Croucher Foundation Grant (CAS20403). X.W. discloses support for the research described in this study from the National Natural Science Foundation of China (62125307). We also disclose support from the SIAT-CUHK Joint Laboratory of Robotics and Intelligent Systems and the Multi-scale Medical Robotics Centre (MRC), InnoHK, at the Hong Kong Science Park.

Author information

Author notes

  1. These authors contributed equally: Ben Wang, Jie Shen, Chenyang Huang.

Authors and Affiliations

  1. College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, P. R. China

    Ben Wang, Zhicheng Ye & Jiajun He

  2. Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, P. R. China

    Jie Shen

  3. Guangdong Provincial Key Laboratory of Robotics and Intelligent System, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P. R. China

    Chenyang Huang, Xinyu Wu & Tiantian Xu

  4. Hubei Collaborative Innovation Centre for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei University, Wuhan, P. R. China

    Zhiguang Guo

  5. Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong SAR, P. R. China

    Li Zhang

  6. The Key Laboratory of Biomedical Imaging Science and System, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P. R. China

    Tiantian Xu

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Contributions

Conceptualization, B.W., L.Z. and T.X.; methodology, B.W., J.S. and C.H.; investigation, B.W., J.S., C.H., Z.Y. and J.H.; supervision, B.W., L.Z. and T.X.; writing—original draft, B.W. and C.H.; writing—review and editing, B.W., J.S., L.Z., X.W., Z.G. and T.X.; funding acquisition, B.W., J.S., Z.Y., L.Z. and T.X.

Corresponding authors

Correspondence to Ben Wang, Li Zhang or Tiantian Xu.

Ethics declarations

Competing interests

B.W. is an inventor with a Chinese patent (patent number ZL202111388615.2, filed on 22 November 2021) on the fabrication method of a magnetic biodegradable blood hydrogel. The other authors declare no competing interests.

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Nature Biomedical Engineering thanks Qiang He, Christopher Nguyen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary notes, figures, tables, references and video captions.

Reporting Summary

Supplementary Video 1

Multimodal locomotion of BBHFs.

Supplementary Video 2

Motion of BBHFs in confined environments.

Supplementary Video 3

Motion of BBHF in a brain phantom.

Supplementary Video 4

Motion through the porcine cerebral cortex with gullies.

Supplementary Video 5

Splitting and drug release process of a BBHF.

Source data

Source Data Figs. 2–5 and 7

Source data for Figs. 2–5 and 7.

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Wang, B., Shen, J., Huang, C. et al. Magnetically driven biohybrid blood hydrogel fibres for personalized intracranial tumour therapy under fluoroscopic tracking. Nat. Biomed. Eng 9, 1471–1485 (2025). https://doi.org/10.1038/s41551-025-01382-z

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