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Bioorthogonal catalytic patch

Nature Nanotechnology volume 16, pages 933–941 (2021)Cite this article

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Abstract

Bioorthogonal catalysis mediated by transition metals has inspired a new subfield of artificial chemistry complementary to enzymatic reactions, enabling the selective labelling of biomolecules or in situ synthesis of bioactive agents via non-natural processes. However, the effective deployment of bioorthogonal catalysis in vivo remains challenging, mired by the safety concerns of metal toxicity or complicated procedures to administer catalysts. Here, we describe a bioorthogonal catalytic device comprising a microneedle array patch integrated with Pd nanoparticles deposited on TiO2 nanosheets. This device is robust and removable, and can mediate the local conversion of caged substrates into their active states in high-level living systems. In particular, we show that such a patch can promote the activation of a prodrug at subcutaneous tumour sites, restoring its parent drug’s therapeutic anticancer properties. This in situ applied device potentiates local treatment efficacy and eliminates off-target prodrug activation and dose-dependent side effects in healthy organs or distant tissues.

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Fig. 1: Design of the microneedle patch and characterization of the Pd–TiO2 nanofillers.
Fig. 2: Characterization of PT-MNs.
Fig. 3: PT-MN-mediated bioorthogonal catalysis in cellular culture.
Fig. 4: PT-MN-mediated prodrug activation in vitro.
Fig. 5: PT-MN-mediated prodrug activation in vivo for anticancer studies.
Fig. 6: Drug and prodrug concentrations versus time and Pd content in tissues after different treatments.

Data availability

All data generated or analysed during this study are included in this published article (and its Supplementary Information files) or are available from the authors upon request.

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Acknowledgements

This work was supported by grants from the start-up packages of the University of North Carolina and North Carolina State University (Z.G.), the University of California at Los Angeles (Z.G.), Zhejiang University (Z.G.) and Fuzhou University (0041-510889, Z.C.); a Sloan Research Fellowship of the Alfred P. Sloan Foundation (Z.G.); and the Jonsson Comprehensive Cancer Center at the University of California at Los Angeles (Z.G.). Part of this work was performed at the Analytical Instrumentation Facility at North Carolina State University, which is supported by the state of North Carolina and the National Science Foundation (grant no. 1542015). The Analytical Instrumentation Facility is a member of the North Carolina Research Triangle Nanotechnology Network, a site in the National Nanotechnology Coordinated Infrastructure. We thank L. Huang from the University of North Carolina at Chapel Hill and Z. Li from Hebei University for providing bioluminescent B16-F10 cells and B16-RFP cells, respectively. The XANES and EXAFS studies of this work used resources of the Advanced Photon Source, an Office of Science User Facility operated for the US Department of Energy Office of Science by Argonne National Laboratory, and was supported by the US Department of Energy under contract no. DE-AC02-06CH11357 and by the Canadian Light Source and its funding partners.

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Author notes

  1. These authors contributed equally: Zhaowei Chen, Hongjun Li.

Authors and Affiliations

  1. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P. R. China

    Zhaowei Chen, Hongjun Li, Jinqiang Wang & Zhen Gu

  2. Institute of Food Safety and Environment Monitoring, College of Chemistry, Fuzhou University, Fuzhou, P. R. China

    Zhaowei Chen

  3. Department of Bioengineering, University of California, Los Angeles, CA, USA

    Zhaowei Chen, Hongjun Li, Zejun Wang, Guojun Chen, Xudong Zhang, Di Wen, Jinqiang Wang, Yi Zeng, Peter Abdou, Jun Fang, Song Li & Zhen Gu

  4. California NanoSystems Institute, University of California, Los Angeles, CA, USA

    Zhaowei Chen, Hongjun Li, Zejun Wang, Guojun Chen, Xudong Zhang, Di Wen, Jinqiang Wang, Yi Zeng, Peter Abdou, Song Li & Zhen Gu

  5. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA

    Zhaowei Chen, Guojun Chen, Xudong Zhang, Di Wen, Jinqiang Wang & Zhen Gu

  6. Zhejiang Laboratory of Systems and Precision Medicine, Zhejiang University Medical Center, Hangzhou, P. R. China

    Hongjun Li & Zhen Gu

  7. College of Biological Science and Engineering, Fuzhou University, Fuzhou, P. R. China

    Yijie Bian & Yimin Miao

  8. Materials Science Division, Argonne National Laboratory, Lemont, IL, USA

    Gang Wan

  9. Center for Minimally Invasive Therapeutics, University of California, Los Angeles, CA, USA

    Song Li & Zhen Gu

  10. Advanced Photon Source, Argonne National Laboratory, Lemont, IL, USA

    Cheng-Jun Sun

  11. Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA

    Zhen Gu

  12. Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, P. R. China

    Zhen Gu

  13. MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, P. R. China

    Zhen Gu

Authors
  1. Zhaowei Chen
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Contributions

Z.C. and Z.G. designed the project. Z.C., H.L., Y.B., Z.W., G.C., X.Z., Y.M., D.W., J.W., G.W., C.-J.S., J.F. and Y.Z. performed the experiments. Z.C., H.L., Y.B., G.C., Y.M., D.W., J.W., G.W. and Z.G. analysed the data. Z.C., H.L., Y.B., Z.W., Y.M., P.A., S.L. and Z.G. wrote the paper.

Corresponding author

Correspondence to Zhen Gu.

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Competing interests

Z.G. and Z.C. have applied for patents related to this study. Z.G. is a scientific cofounder of ZenCapsule and ZCapsule. The other authors declare no competing interests.

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Chen, Z., Li, H., Bian, Y. et al. Bioorthogonal catalytic patch. Nat. Nanotechnol. 16, 933–941 (2021). https://doi.org/10.1038/s41565-021-00910-7

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