Bioorthogonal catalytic patch

Zhaowei Chen; Hongjun Li; Yijie Bian; Zejun Wang; Guojun Chen; Xudong Zhang; Yimin Miao; Di Wen; Jinqiang Wang; Gang Wan; Yi Zeng; Peter Abdou; Jun Fang; Song Li; Cheng-Jun Sun; Zhen Gu

doi:10.1038/s41565-021-00910-7

Bioorthogonal catalytic patch

Nat Nanotechnol. 2021 Aug;16(8):933-941. doi: 10.1038/s41565-021-00910-7. Epub 2021 May 10.

Authors

Zhaowei Chen^#^{1

2

3

4

5}, Hongjun Li^#^{1

3

4

6}, Yijie Bian⁷, Zejun Wang^{3

4}, Guojun Chen^{3

4

5}, Xudong Zhang^{3

4

5}, Yimin Miao⁷, Di Wen^{3

4

5}, Jinqiang Wang^{1

3

4

5}, Gang Wan⁸, Yi Zeng^{3

4}, Peter Abdou^{3

4}, Jun Fang³, Song Li^{3

4

9}, Cheng-Jun Sun¹⁰, Zhen Gu^{11

12

13

14

15

16

17

18

19}

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.

PMID: 33972760
DOI: 10.1038/s41565-021-00910-7

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacokinetics
Antineoplastic Agents* / pharmacology
Catalysis
Drug Delivery Systems*
Hep G2 Cells
Humans
Melanoma, Experimental
Metal Nanoparticles* / chemistry
Metal Nanoparticles* / therapeutic use
Mice
Palladium* / chemistry
Palladium* / pharmacokinetics
Palladium* / pharmacology
Prodrugs* / chemistry
Prodrugs* / pharmacokinetics
Prodrugs* / pharmacology
Titanium* / chemistry
Titanium* / pharmacokinetics
Titanium* / pharmacology

Substances

Antineoplastic Agents
Prodrugs
titanium dioxide
Palladium
Titanium