单原子催化剂的生物医学应用研究进展

doi:10.3969/j.issn.1674-8115.2022.12.014

摘要/Abstract

摘要：

随着纳米技术和材料科学的快速发展，许多根据疾病的微环境理化特性进行设计和改造的纳米材料，通过特定刺激触发原位催化反应，已被证实具有有效的治疗作用。然而，针对目前纳米医学应用的催化剂存在结构复杂和潜在的金属离子毒性问题，研究者们致力于开发和改进合成更有效、更可控和毒性更低的纳米催化剂。近年来，单原子催化剂（single-atom catalysts，SACs）作为锚定或配位在合适载体上的原子分散的金属活性位点，具有优异催化活性和高选择性，显示出在治疗应用中的巨大潜力。该文概述了SACs在生物医学应用方面的开发进展，重点阐述了在抗菌、癌症治疗、氧化应激细胞保护和生物传感方面应用的最新进展，通过列举成功研制的一系列代表性SACs揭示其在不同疾病应用的催化触发机制，了解潜在的结构与性能关系。最后，对SACs在纳米催化医学领域面临的当前挑战和未来机遇进行了探讨和展望。

关键词: 单原子催化剂, 生物医学应用, 酶样反应, 纳米医学, 生物催化机制

Abstract:

With the rapid advances in nanotechnology and materials science, lots of nanomaterials designed and modified according to the pathophysiological and chemical properties of the disease microenvironment have been proven to achieve effective therapeutic effects by triggering in situ catalytic reactions through specific stimuli. However, in response to the structural complexity and potential metal ion toxicity of current catalysts for nanomedical applications, researchers have worked to develop and improve the synthesis of nanocatalysts which are significantly more effective, more controllable and less toxic. In recent years, single-atom catalysts (SACs) show great potential for therapeutic applications as atomically dispersed metal active sites, anchored or coordinated on suitable carriers with excellent catalytic activity and high selectivity. This review provides an outline of the progress in development of SACs for biomedical applications, focusing on recent advances in applications encompassing antimicrobial, cancer therapy, oxidative-stress cytoprotection and biosensing, and revealing the catalytic triggering mechanisms of SACs for different disease applications by citing a series of successfully established representative examples and understanding the structure-property relationships. Finally, current challenges and future perspectives for the engineering of SACs in noncatalytic medicine are also discussed and outlooked.

Key words: single-atom catalysts, biomedical application, enzyme-like reaction, nanomedicine, biocatalytic mechanism

中图分类号:

O643.32

谢玉婷, 熊屏. 单原子催化剂的生物医学应用研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(12): 1751-1756.

XIE Yuting, XIONG Ping. Research advances in biomedical applications of single-atom catalysts[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(12): 1751-1756.

参考文献 65

1	ZHU W, CHEN Z, PAN Y, et al. Functionalization of hollow nanomaterials for catalytic applications: nanoreactor construction[J]. Adv Mater, 2019, 31(38): e1800426.
2	SU K, TAN L, LIU X M, et al. Rapid photo-sonotherapy for clinical treatment of bacterial infected bone implants by creating oxygen deficiency using sulfur doping[J]. ACS Nano, 2020, 14(2): 2077-2089.
3	ZHU X F, GONG Y C, LIU Y N, et al. Ru@CeO2 yolk shell nanozymes: oxygen supply in situ enhanced dual chemotherapy combined with photothermal therapy for orthotopic/subcutaneous colorectal cancer[J]. Biomaterials, 2020, 242: 119923.
4	ZHANG Y, HU H P, TANG W Q, et al. A multifunctional magnetic nanosystem based on "two strikes" effect for synergistic anticancer therapy in triple-negative breast cancer[J]. J Control Release, 2020, 322: 401-415.
5	SAHU A, KWON I, TAE G. Improving cancer therapy through the nanomaterials-assisted alleviation of hypoxia[J]. Biomaterials, 2020, 228: 119578.
6	FAN Y, LIU S G, YI Y, et al. Catalytic nanomaterials toward atomic levels for biomedical applications: from metal clusters to single-atom catalysts[J]. ACS Nano, 2021, 15(2): 2005-2037.
7	CHONG Y, LIU Q, GE C C. Advances in oxidase-mimicking nanozymes: classification, activity regulation and biomedical applications[J]. Nano Today, 2021, 37: 101076.
8	HUANG Y Y, REN J S, QU X G. Nanozymes: classification, catalytic mechanisms, activity regulation, and applications[J]. Chem Rev, 2019, 119(6): 4357-4412.
9	WU J, WANG X Y, WANG Q, et al. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (Ⅱ)[J]. Chem Soc Rev, 2019, 48(4): 1004-1076.
10	YANG Y, ZHANG C, LAI C, et al. BiOX (X = Cl, Br, I) photocatalytic nanomaterials: applications for fuels and environmental management[J]. Adv Colloid Interface Sci, 2018, 254: 76-93.
11	HU W H, ZHENG M B, XU B Y, et al. Design of hollow carbon-based materials derived from metal-organic frameworks for electrocatalysis and electrochemical energy storage[J]. J Mater Chem A, 2021, 9(7): 3880-3917.
12	YANG W, WANG L, METTENBRINK E M, et al. Nanoparticle toxicology[J]. Annu Rev Pharmacol Toxicol, 2021, 61: 269-289.
13	WANG H, WAN K, SHI X. Recent advances in nanozyme research[J]. Adv Mater, 2019, 31(45): e1805368.
14	HUANG L, CHEN J, GAN L, et al. Single-atom nanozymes[J]. Sci Adv, 2019, 5(5): eaav5490.
15	LI L L, CHANG X, LIN X Y, et al. Theoretical insights into single-atom catalysts[J]. Chem Soc Rev, 2020, 49(22): 8156-8178.
16	KAISER S K, CHEN Z P, FAUST AKL D, et al. Single-atom catalysts across the periodic table[J]. Chem Rev, 2020, 120(21): 11703-11809.
17	JI S F, JIANG B, HAO H G, et al. Matching the kinetics of natural enzymes with a single-atom iron nanozyme[J]. Nat Catal, 2021, 4(5): 407-417.
18	SULTAN S, TIWARI J N, SINGH A N, et al. Single atoms and clusters based nanomaterials for hydrogen evolution, oxygen evolution reactions, and full water splitting[J]. Adv Energy Mater, 2019, 9(22): 1900624.
19	XIANG H J, FENG W, CHEN Y. Single-atom catalysts in catalytic biomedicine[J]. Adv Mater, 2020, 32(8): e1905994.
20	NIKOLOVA M P, CHAVALI M S. Metal oxide nanoparticles as biomedical materials[J]. Biomimetics (Basel), 2020, 5(2): 27.
21	MEADE E, SLATTERY M A, GARVEY M. Bacteriocins, potent antimicrobial peptides and the fight against multi drug resistant species: resistance is futile? [J]. Antibiotics (Basel), 2020, 9(1): 32.
22	TAN P, FU H Y, MA X. Design, optimization, and nanotechnology of antimicrobial peptides: from exploration to applications[J]. Nano Today, 2021, 39: 101229.
23	URUÉN C, CHOPO-ESCUIN G, TOMMASSEN J, et al. Biofilms as promoters of bacterial antibiotic resistance and tolerance[J]. Antibiotics (Basel), 2020, 10(1): 3.
24	HUO J J, JIA Q Y, HUANG H, et al. Emerging photothermal-derived multimodal synergistic therapy in combating bacterial infections[J]. Chem Soc Rev, 2021, 50(15): 8762-8789.
25	CHEESEMAN S, CHRISTOFFERSON A J, KARIUKI R, et al. Antimicrobial metal nanomaterials: from passive to stimuli-activated applications[J]. Adv Sci (Weinh), 2020, 7(10): 1902913.
26	XIN Q, SHAH H, NAWAZ A, et al. Antibacterial carbon-based nanomaterials[J]. Adv Mater, 2019, 31(45): e1804838.
27	XU B L, WANG H, WANG W W, et al. A single-atom nanozyme for wound disinfection applications[J]. Angew Chem Int Ed Engl, 2019, 58(15): 4911-4916.
28	HUO M F, WANG L Y, ZHANG H X, et al. Construction of single-iron-atom nanocatalysts for highly efficient catalytic antibiotics[J]. Small, 2019, 15(31): e1901834.
29	WANG X W, SHI Q Q, ZHA Z B, et al. Copper single-atom catalysts with photothermal performance and enhanced nanozyme activity for bacteria-infected wound therapy[J]. Bioact Mater, 2021, 6(12): 4389-4401.
30	YANG B W, CHEN Y, SHI J L. Nanocatalytic medicine[J]. Adv Mater, 2019, 31(39): 1901778.
31	WANG L Y, HUO M F, CHEN Y, et al. Tumor microenvironment-enabled nanotherapy[J]. Adv Healthc Mater, 2018, 7(8): e1701156.
32	RANJI-BURACHALOO H, GURR P A, DUNSTAN D E, et al. Cancer treatment through nanoparticle-facilitated Fenton reaction[J]. ACS Nano, 2018, 12(12): 11819-11837.
33	QI C, HE J, FU L H, et al. Tumor-specific activatable nanocarriers with gas-generation and signal amplification capabilities for tumor theranostics[J]. ACS Nano, 2021, 15(1): 1627-1639.
34	HAN D L, HAN Y J, LI J, et al. Enhanced photocatalytic activity and photothermal effects of cu-doped metal-organic frameworks for rapid treatment of bacteria-infected wounds[J]. Appl Catal B Environ, 2020, 261: 118248.
35	ZHANG N Q, ZHANG X X, KANG Y K, et al. A supported Pd2 dual-atom site catalyst for efficient electrochemical CO₂ reduction[J]. Angew Chem Int Ed Engl, 2021, 60(24): 13388-13393.
36	LU X Y, GAO S S, LIN H, et al. Bioinspired copper single-atom catalysts for tumor parallel catalytic therapy[J]. Adv Mater, 2020, 32(36): e2002246.
37	ZAKHARCHENKO A, GUZ N, LARADJI A M, et al. Magnetic field remotely controlled selective biocatalysis[J]. Nat Catal, 2018, 1(1): 73-81.
38	FENG L, GAI S, DAI Y, et al. Controllable generation of free radicals from multifunctional heat-responsive nanoplatform for targeted cancer therapy [J]. Chem Mater, 2018, 30(2): 526-539.
39	JIANG R M, DAI J, DONG X Q, et al. Improving image-guided surgical and immunological tumor treatment efficacy by photothermal and photodynamic therapies based on a multifunctional NIR AIEgen[J]. Adv Mater, 2021, 33(22): e2101158.
40	DENG X Y, SHAO Z W, ZHAO Y L. Solutions to the drawbacks of photothermal and photodynamic cancer therapy[J]. Adv Sci (Weinh), 2021, 8(3): 2002504.
41	CHEN J M, FAN T J, XIE Z J, et al. Advances in nanomaterials for photodynamic therapy applications: status and challenges[J]. Biomaterials, 2020, 237: 119827.
42	LI X S, LOVELL J F, YOON J, et al. Clinical development and potential of photothermal and photodynamic therapies for cancer[J]. Nat Rev Clin Oncol, 2020, 17(11): 657-674.
43	WANG D D, WU H H, PHUA S Z F, et al. Self-assembled single-atom nanozyme for enhanced photodynamic therapy treatment of tumor[J]. Nat Commun, 2020, 11(1): 357.
44	WANG L, QU X Z, ZHAO Y X, et al. Exploiting single atom iron centers in a porphyrin-like MOF for efficient cancer phototherapy[J]. ACS Appl Mater Interfaces, 2019, 11(38): 35228-35237.
45	LIANG S, DENG X R, MA P A, et al. Recent advances in nanomaterial-assisted combinational sonodynamic cancer therapy[J]. Adv Mater, 2020, 32(47): e2003214.
46	PAN X T, BAI L X, WANG H, et al. Metal-organic-framework-derived carbon nanostructure augmented sonodynamic cancer therapy[J]. Adv Mater, 2018, 30(23): e1800180.
47	CHENG X T, XU H D, RAN H H, et al. Glutathione-depleting nanomedicines for synergistic cancer therapy[J]. ACS Nano, 2021, 15(5): 8039-8068.
48	WANG M, CHANG M Y, CHEN Q, et al. Au2Pt-PEG-Ce6 nanoformulation with dual nanozyme activities for synergistic chemodynamic therapy/phototherapy[J]. Biomaterials, 2020, 252: 120093.
49	HUO M F, WANG L Y, WANG Y W, et al. Nanocatalytic tumor therapy by single-atom catalysts[J]. ACS Nano, 2019, 13(2): 2643-2653.
50	ZHU Y, WANG W Y, CHENG J J, et al. Stimuli-responsive manganese single-atom nanozyme for tumor therapy via integrated cascade reactions[J]. Angew Chem Int Ed Engl, 2021, 60(17): 9480-9488.
51	DU F X, LIU L C, WU Z H, et al. Pd-single-atom coordinated biocatalysts for chem-/ sono-/ photo-trimodal tumor therapies[J]. Adv Mater, 2021, 33(29): e2101095.
52	LI Q, LIU Y, DAI X L, et al. Nanozymes regulate redox homeostasis in ROS-related inflammation[J]. Front Chem, 2021, 9: 740607.
53	YU H, JIN F Y, LIU D, et al. ROS-responsive nano-drug delivery system combining mitochondria-targeting ceria nanoparticles with atorvastatin for acute kidney injury[J]. Theranostics, 2020, 10(5): 2342-2357.
54	ZHENG L M, YU P J, ZHANG Y B, et al. Evaluating the bio-application of biomacromolecule of lignin-carbohydrate complexes (LCC) from wheat straw in bone metabolism via ROS scavenging[J]. Int J Biol Macromol, 2021, 176: 13-25.
55	SAUNDERS R M, BIDDLE M, AMRANI Y, et al. Stressed out - The role of oxidative stress in airway smooth muscle dysfunction in asthma and COPD[J]. Free Radic Biol Med, 2022, 185: 97-119.
56	LIU T F, XIAO B W, XIANG F, et al. Ultrasmall copper-based nanoparticles for reactive oxygen species scavenging and alleviation of inflammation related diseases[J]. Nat Commun, 2020, 11(1): 2788.
57	HUANG X, HE D, PAN Z, et al. Reactive-oxygen-species-scavenging nanomaterials for resolving inflammation[J]. Mater Today Bio, 2021, 11: 100124.
58	MA W J, MAO J J, YANG X T, et al. A single-atom Fe-N4 catalytic site mimicking bifunctional antioxidative enzymes for oxidative stress cytoprotection[J]. Chem Commun (Camb), 2018, 55(2): 159-162.
59	YAN R J, SUN S, YANG J, et al. Nanozyme-based bandage with single-atom catalysis for brain trauma[J]. ACS Nano, 2019, 13(10): 11552-11560.
60	BHALLA N, PAN Y W, YANG Z G, et al. Opportunities and challenges for biosensors and nanoscale analytical tools for pandemics: covid-19[J]. ACS Nano, 2020, 14(7): 7783-7807.
61	ZHANG S Y, WONG C L, ZENG S W, et al. Metasurfaces for biomedical applications: imaging and sensing from a nanophotonics perspective[J]. Nanophotonics, 2020, 10(1): 259-293.
62	ZHOU M, JIANG Y, WANG G, et al. Single-atom Ni-N4 provides a robust cellular NO sensor[J]. Nat Commun, 2020, 11(1): 3188.
63	JING W J, CUI X K, KONG F B, et al. Fe-N/C single-atom nanozyme-based colorimetric sensor array for discriminating multiple biological antioxidants[J]. Analyst, 2021, 146(1): 207-212.
64	YAMADA T, KOJIMA T, ABE E, et al. Probing single Pt atoms in complex intermetallic Al13Fe4[J]. J Am Chem Soc, 2018, 140(11): 3838-3841.
65	SHI J J, KANTOFF P W, WOOSTER R, et al. Cancer nanomedicine: progress, challenges and opportunities[J]. Nat Rev Cancer, 2017, 17(1): 20-37.