1. Academic Validation
  2. Bioorthogonal catalytic patch

Bioorthogonal catalytic patch

  • Nat Nanotechnol. 2021 Aug;16(8):933-941. doi: 10.1038/s41565-021-00910-7.
Zhaowei Chen # 1 2 3 4 5 Hongjun Li # 1 3 4 6 Yijie Bian 7 Zejun Wang 3 4 Guojun Chen 3 4 5 Xudong Zhang 3 4 5 Yimin Miao 7 Di Wen 3 4 5 Jinqiang Wang 1 3 4 5 Gang Wan 8 Yi Zeng 3 4 Peter Abdou 3 4 Jun Fang 3 Song Li 3 4 9 Cheng-Jun Sun 10 Zhen Gu 11 12 13 14 15 16 17 18 19
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P. R. China.
  • 2 Institute of Food Safety and Environment Monitoring, College of Chemistry, Fuzhou University, Fuzhou, P. R. China.
  • 3 Department of Bioengineering, University of California, Los Angeles, CA, USA.
  • 4 California NanoSystems Institute, University of California, Los Angeles, CA, USA.
  • 5 Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA.
  • 6 Zhejiang Laboratory of Systems and Precision Medicine, Zhejiang University Medical Center, Hangzhou, P. R. China.
  • 7 College of Biological Science and Engineering, Fuzhou University, Fuzhou, P. R. China.
  • 8 Materials Science Division, Argonne National Laboratory, Lemont, IL, USA.
  • 9 Center for Minimally Invasive Therapeutics, University of California, Los Angeles, CA, USA.
  • 10 Advanced Photon Source, Argonne National Laboratory, Lemont, IL, USA.
  • 11 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P. R. China. guzhen@zju.edu.cn.
  • 12 Department of Bioengineering, University of California, Los Angeles, CA, USA. guzhen@zju.edu.cn.
  • 13 California NanoSystems Institute, University of California, Los Angeles, CA, USA. guzhen@zju.edu.cn.
  • 14 Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. guzhen@zju.edu.cn.
  • 15 Zhejiang Laboratory of Systems and Precision Medicine, Zhejiang University Medical Center, Hangzhou, P. R. China. guzhen@zju.edu.cn.
  • 16 Center for Minimally Invasive Therapeutics, University of California, Los Angeles, CA, USA. guzhen@zju.edu.cn.
  • 17 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA. guzhen@zju.edu.cn.
  • 18 Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, P. R. China. guzhen@zju.edu.cn.
  • 19 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, P. R. China. guzhen@zju.edu.cn.
  • # Contributed equally.
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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