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化学进展 2022, Vol. 34 Issue (9): 2035-2050 DOI: 10.7536/PC211110 前一篇   后一篇

• 综述 •

生物酶驱动的微纳米马达在生物医学领域的应用

张荡, 王曦, 王磊*()   

  1. 哈尔滨工业大学化工与化学学院 新能源转换与储存关键材料技术工业和信息化部重点实验室 哈尔滨 150001
  • 收稿日期:2021-11-10 修回日期:2021-12-01 出版日期:2022-09-20 发布日期:2022-04-01
  • 基金资助:
    国家自然科学基金项目(52073071); 国家自然科学基金项目(51703043); 国家重点研发计划(2021YFF0603500); 国家博士后项目(2020T130144); 国家博士后项目(2016M600247); 黑龙江省自然科学基金项目(YQ2022E021)
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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:2021-11-10 Revised:2021-12-01 Online:2022-09-20 Published:2022-04-01
  • 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)

生物酶驱动微纳米马达是指利用天然酶催化分解过氧化氢、葡萄糖、尿素和甘油酯等燃料来提供动力的一种新型微纳米机器。生物酶驱动的微纳米马达具有良好的生物相容性,能够在原位利用生物燃料实现自主靶向运动,无需外加原料,这使得生物酶驱动的微纳米马达在生物医学领域展现出巨大的发展潜力与前景。目前,生物酶驱动的微纳米马达在生物医学领域的应用得到众多科学家的关注,但是时至今日,还没有一篇及时、全面、着重地讨论生物酶驱动微纳米马达在生物医学领域应用的综述文章。基于本课题组的研究经验以及目前该领域的发展情况,本文着重讨论不同种类生物酶驱动微纳米马达在疾病诊疗等生物医学领域应用的最新进展,包括生物标志物的检测与诊断、成像显像剂、癌症和其他疾病的治疗等。最后,本文对该领域的发展与未来研究方向提出展望,为实现以“面向世界科技前沿、面向人民生命健康”为目标的“人类卫生健康共同体”提供新的思路和方向。

关键词： 微纳米马达, 酶催化, 癌症治疗, 生物成像

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
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图1 注入LMs后小鼠膀胱的US和PA图像[31]
Fig. 1 US and PA images of a mouse bladder after LMs injection, Copyright © 2021, American Chemical Society, reproduced with permission Ref.[31]
图2 用于DNA分子检测的各种微纳米马达[38⇓⇓~41]
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
图3 多功能Janus粒子快速检测PCT示意图[44]:(A)多功能Janus粒子检测PCT的机理;(B)快速检测降钙素原的可视化策略
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]
图4 捕获CTC的JMs示意图[47] :(A) JMs 捕获CTC机理。(B) 捕获 HepG2 细胞后 JM-2 的 SEM 图像。(C) JMs定量检测HepG2细胞
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
表1 生物酶驱动微纳米马达在疾病诊断中的代表示例
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
图5 过氧化氢酶驱动马达的药物释放示意图[59,61⇓~63]
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
图6 尿素酶驱动的纳米马达用于药物释放和肿瘤破碎[71,72]
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
图7 尿素酶驱动的纳米马达增强膀胱内药物渗透和滞留的示意图[74]
Fig. 7 Schematic illustration of urease-driven nanomotor enhancing drug penetration and retention in bladder[74]. Copyright © 2020 American Chemical Society
图8 小鼠静脉注射18F-标记的尿素酶-AuNP纳米马达[76]
Fig. 8 Mice intravenously injected with18F labeled urease AuNP nanomotor[76],Copyright ©2021 American Association for the Advancement of Science
图9 微纳米马达选择性结合细胞受体的示意图[87]
Fig. 9 Schematic representation of the proposed method for selectively binding cell receptors[87].Copyright © 2017 The Royal Society of Chemistry
图10 UTZCG 纳米马达制造和协同光动力饥饿疗法的过程[92]
Fig. 10 Fabrication of UTZCG nanomotors and collaborative photodynamic starvation therapy via self-accelerating cascade reactions[92].Copyright@© 2019 Elsevier
图11 脂肪酶驱动微纳米马达的制备、运动能力及三丁酸甘油酯液滴的动态降解过程[95]
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
图12 (A)尿素酶驱动微纳米马达的示意图、(B)口服递送微纳米马达在胃中的增强渗透和滞留及(C)染色组织学分析[101]
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
表2 利用生物酶驱动的微纳米马达治疗各种疾病的代表示例
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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