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Progress in Chemistry 2022, Vol. 34 Issue (9): 2035-2050 DOI: 10.7536/PC211110 Previous Articles   Next Articles

• Review •

Biomedical Applications of Enzyme-Powered Micro/Nanomotors

Dang Zhang, Xi Wang, Lei Wang()   

  1. School of Chemistry and Chemical Engineering, Key Laboratory of New Energy Conversion and Storage Key Material of Ministry of Industry and Information Technology, Harbin Institute of Technology,Harbin 150001, China
  • Received: Revised: Online: Published:
  • Contact: *e-mail: leiwang_chem@hit.edu.cn
  • About author:
    †These authors contributed equally to this work.
  • Supported by:
    National Natural Science Foundation of China(52073071); National Natural Science Foundation of China(51703043); National Key R&D Program of China(2021YFF0603500); National Postdoctoral Program(2020T130144); National Postdoctoral Program(2016M600247); Natural Science Foundation of Heilongjiang Province(YQ2022E021)
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Enzyme-powered micro/nanomotor is a new type of micro/nanomachines that uses natural enzymes to catalyze the decomposition of fuels such as hydrogen peroxide, glucose, urea, and glycerides to provide power, which mainly includes hydrogen peroxidase, urease, glucose oxidase, and lipase-powered nanomotors. Compared with traditional micro/nanomotors, enzyme powered micro/nanomotors have good biocompatibility, and can achieve autonomous targeting motion in situ using biofuel without additional fuels, which endows enzyme-driven micro/nanomotors with great potential and prospects for in vivo applications, especially in biomedical fields. Currently, the application of enzyme-driven micro/nanomotors in biomedical fields has attracted the attention of many researchers. However, there is no review timely and concisely summarizing the progress in this research aspect. Therefore, based on our experience, this paper focuses on the recent progress of different types of enzyme-powered micro/nanomotors in cancer diagnosis and treatment, and briefly introduces the application of triglyceride degradation and bacterial infection. Finally, this paper provides an outlook on the development and future research in this field, and hopes to stimulate new ideas for building a "human health community" with the goal of "towards the science and technology frontiers worldwide, as well as peoples’ life and health".

Contents

1 Introduction

2 Application of enzyme-driven micro/nanomotors in disease detection and diagnosis

2.1 Bioimaging agents

2.2 Molecular marker detection

3 Applications of enzyme-driven micro/nanomotors in disease treatment

3.1 Cancer treatment

3.2 Treatment of other diseases

4 Conclusions and outlook

Key words: micro/nanomotors, enzymatic catalysis, cancer therapy, bioimaging
Fig. 1 US and PA images of a mouse bladder after LMs injection, Copyright © 2021, American Chemical Society, reproduced with permission Ref.[31]
Fig. 2 Micro/nanomotors for DNA molecular detection[38⇓⇓~41]. (A) Copyright © 2019 American Chemical Society. (B) Copyright © The Royal Society of Chemistry 2017. (C) Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. (D) Copyright © 2016 Elsevier
Fig. 3 Scheme of rapid detection of PCT by multifunction Janus particle[44]: (A)Mechanism of detection of PCT by multifunctional Janus particle. (B)Visual strategy for rapid detection of procalcitonin. Copyright © 2019 Elsevier[44]
Fig. 4 Scheme of JMs after capture of CTC[47] : (A) Mechanism for JMs to capture CTC. (B) SEM image of JM-2 after capture of HepG2 cells. (C) Quantitative detection of HepG2 cells by JMs, Copyright © 2019 Elsevier
Table 1 Summary of the representative examples in the diagnosis based on enzyme-powered micro/nanomotors
Types of EMNMs Materials Fuel Velocity and medium Application ref
Urease Ga-In-Sn Urea — Targeted transportation;
Synergetic therapy;Imaging		 31
Catalase Au-Pt H2O2 — Imaging agents 32
Au/Ag/Ni/DNA H2O2 209 μm/s (1.5% H2O2) Biosensing 38
PEDOT-PSS/Au/DNA H2O2 420 μm/s (2% H2O2 ) DNA detection 39
SiO2/ Oligonucleotide H2O2 — Target recognition;Cargo transport 40
PEDOT/Au H2O2 411±40 μm/s(5% H2O2) DNA detection 41
Iron oxide H2O2 — Biosensing 44
Janus fibers H2O2 42 μm/s (3.5% H2O2) Capture of circulating tumor cell 47
Fig. 5 Drug release mechanism of the micro/nanomotors powered by catalase[59,61⇓~63]. Ref 59 Copyright © 2019 American Chemical Society; Ref 61,62 Copyright © 2014 American Chemical Society; Ref 63 © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Fig. 6 Urease-powered nanomotors used for drug delivery and tumor therapy[71,72].Ref 71 Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim; Ref 72 Copyright © 2018 American Chemical Society
Fig. 7 Schematic illustration of urease-driven nanomotor enhancing drug penetration and retention in bladder[74]. Copyright © 2020 American Chemical Society
Fig. 8 Mice intravenously injected with18F labeled urease AuNP nanomotor[76],Copyright ©2021 American Association for the Advancement of Science
Fig. 9 Schematic representation of the proposed method for selectively binding cell receptors[87].Copyright © 2017 The Royal Society of Chemistry
Fig. 10 Fabrication of UTZCG nanomotors and collaborative photodynamic starvation therapy via self-accelerating cascade reactions[92].Copyright@© 2019 Elsevier
Fig. 11 Preparation and motility of lipase driven micro/nanomotor and dynamic degradation process of triglyceride droplets[95]. Copyright © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Fig. 12 (A) Schematic diagram of urease-driven micro/nanomotors, (B) enhanced infiltration and retention of oral delivery micro/nanomotors in the stomach and (C) histological analysis of staining[101].Copyright@© 2021 Elsevier
Table 2 Summary of representative examples for disease treatment using enzyme-powered micro/nanomotors
Types of EMNMs Materials Fuel Velocity and medium Application ref
Catalase Ti/Au-Thiol H2O2 10 body lengths s-1(1.5 wt%) 55
Polydimethyl sulfoxane H2O2 5.2 body lengths s-1(4%) 56
PEG-PS H2O2 117 body lengths s-1 Drug delivery 59
Mesoporous SiO2 H2O2 3.75 μm2/s(6 wt%) Drug delivery 9
Polymer based bottlebrush H2O2 23.6 μm/s (10 mmol·L-1 H2O2 ) Overcoming tissue
Penetration barrier		 60
Bovine serum Albumin/poly-L-lysine (PLL/BSA) multilayer H2O2 68 μm/s (0.5% H2O2) Drug delivery 61
Polymers/Au H2O2 108 μm/s (1% H2O2) Drug delivery 62
MOF H2O2 Drug delivery 63
Urease Tubular SiO2 Urea 66
Mesoporous SiO2 Urea 5 body lengths·s-1
(25 mmol·L-1)		 Drug delivery 67
Mesoporous SiO2 Urea 6.24 μm2·s-1
(10 mmol·L-1)		 Drug delivery 69
Mesoporous SiO2 Urea Drug delivery 70
Mesoporous SiO2/ MSNP-Ur/PEG-Ab Urea Cancer therapy 71
Mesoporous SiO2 Urea 1.36±0.05 μm2/s
300 mmol·L-1 urea PBS		 Drug delivery 72
PDA/SiO2 Urea 10.67 μm/s
(100 mmol·L-1)		 Drug delivery 73
Platelet Urea Drug delivery 74
Protein Urea 2.7±0.2 μm·s-1
100 mmol·L-1 urea PBS		 75
SiO2 Urea Drug delivery 76
GOx SiO2 Glucose 81
GOx+Cat SiO2/PDA
PLL-g-PEG		 Glucose Drug delivery 82
GOx+Cat Polymer vesicle Glucose 176 body lengths·s-1(100 mM) Drug delivery 83
GOx+trypsin Pt/ MF-NPs Glucose Targeted transportation 84
GOx CNF Glucose 85
GOx Au/polymer Glucose 120 body lengths ·s-1 Targeted transportation 86
GOx Nanoparticles Glucose Drug delivery 87
GOx+Cat Polymer vesicle Glucose Drug delivery 88
Lipase SiO2 Triglycerides Biodegradation 95
Lipase SiO2 Triglycerides Biodegradation 96
Lipase SiO2 Triglycerides Biodegradation 97
Lipase PGMA/PS Triglycerides Biodegradation 98
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