Nanozymes with bioorthogonal reaction for intelligence nanorobots

Abstract

Bioorthogonal reactions have attained great interest and achievements in various fields since its first appearance in 2003. Compared to traditional chemical reactions, bioorthogonal chemical reactions mediated by transition metals catalysts can occur under physiological conditions in the living system without interfering with or damaging other biochemical events happening simultaneously. The idea of using nanomachines to perform precise and specific tasks in living systems is regarded as the frontier in nanomedicine. Bioorthogonal chemical reactions and nanozymes have provided new potential and strategies for nanomachines used in biomedical fields such as drug release, imaging, and bioengineering. Nanomachines, also called as intelligence nanorobots, based on nanozymes with bioorthogonal reactions show better biocompatibility and water solubility in living systems and perform controlled and adjustable stimuli-triggered response regarding to different physiological environments. In this review, we review the definition and development of bioorthogonal chemical reactions and describe the basic principle of bioorthogonal nanozymes fabrication. We also review several controlled and adjustable stimuli-triggered intelligence nanorobots and their potential in therapeutic and engineered applications. Furthermore, we summarize the challenges in the use of intelligence nanorobots based on nanozymes with bioorthogonal chemical reactions and propose promising vision in smart nanodevices along this appealing avenue of research.

Graphical abstract

Keywords

Nanozymes / Bioorthogonal reaction / Nanorobotics

References

[1] Adam C , Perez-Lopez AM , Hamilton L , Rubio-Ruiz B , Bray TL , Sieger D , Brennan PM , Unciti-Broceta A . Bioorthogonal uncaging of the active metabolite of irinotecan by palladium-functionalized microdevices. Chemistry, 2018, 24( 63): 16783– 16790

[2] Anhauser L , Huwel S , Zobel T , Rentmeister A . Multiple covalent fluorescence labeling of eukaryotic mRNA at the poly(A) tail enhances translation and can be performed in living cells. Nucleic Acids Res, 2019, 47( 7): e42

[3] Bertozzi CR . A decade of bioorthogonal chemistry. Acc Chem Res, 2011, 44( 9): 651– 653

[4] Bildstein L , Dubernet C , Couvreur P . Prodrug-based intracellular delivery of anticancer agents. Adv Drug Deliver Rev, 2011, 63( 1-2): 3– 23

[5] Boyce M , Bertozzi CR . Bringing chemistry to life. Nat Methods, 2011, 8( 8): 638– 642

[6] Canaparo R , Foglietta F , Giuntini F , Della Pepa C , Dosio F , Serpe L . Recent developments in antibacterial therapy: focus on stimuli-responsive drug-delivery systems and therapeutic nanoparticles. Molecules, 2019, 24( 10): 1991

[7] Cao-Milán R , Gopalakrishnan S , He LD , Huang R , Wang L-S , Castellanos L , Luther DC , Landis RF , Makabenta JMV , Li C-H , Zhang X , Scaletti F , Vachet RW , Rotello VM . Thermally gated bio-orthogonal nanozymes with supramolecularly confined porphyrin catalysts for antimicrobial uses. Chem, 2020, 6( 5): 1113– 1124

[8] Carell T , Vrabel M . Bioorthogonal chemistry-introduction and overview. Top Curr Chem, 2016, 374( 1): 9

[9] Carrico IS , Carlson BL , Bertozzi CR . Introducing genetically encoded aldehydes into proteins. Nat Chem Biol, 2007, 3( 6): 321– 322

[10] Chatterjee A , Ward TR . Recent advances in the palladium catalyzed Suzuki–Miyaura cross-coupling reaction in water. Catal Lett, 2016, 146( 4): 820– 840

[11] Chu Y , Oum YH , Carrico IS . Surface modification via strain-promoted click reaction facilitates targeted lentiviral transduction. Virology, 2016, 487 : 95– 103

[12] Clavadetscher J , Hoffmann S , Lilienkampf A , Mackay L , Yusop RM , Rider SA , Mullins JJ , Bradley M . Copper catalysis in living systems and in situ drug synthesis. Angew Chem Int Ed, 2016, 55( 50): 15662– 15666

[13] Das R , Landis RF , Tonga GY , Cao-Milan R , Luther DC , Rotello VM . Control of intra-versus extracellular bioorthogonal catalysis using surface-engineered nanozymes. ACS Nano, 2019, 13( 1): 229– 235

[14] Destito P , Sousa-Castillo A , Couceiro JR , López F , Mascareñas JL . Hollow nanoreactors for Pd-catalyzed Suzuki−Miyaura couplings and O-propargyl cleavage reactions in bio-relevant aqueous media. Chem Sci, 2019, 10( 9): 2598– 2603

[15] Devaraj NK . The future of bioorthogonal chemistry. ACS Cent Sci, 2018, 4( 8): 952– 959

[16] Dong YS , Tu YL , Wang KW , Xu C , Yuan Y , Wang J . A general strategy for macrotheranostic prodrug activation: synergy between the acidic tumor microenvironment and bioorthogonal chemistry. Angew Chem Int Ed, 2020, 59( 18): 7168– 7172

[17] Eda S , Nasibullin I , Vong K , Kudo N , Yoshida M , Kurbangalieva A , Tanaka K . Biocompatibility and therapeutic potential of glycosylated albumin artificial metalloenzymes. Nat Catal, 2019, 2( 9): 780– 792

[18] Ellen M S . From mechanism to mouse: a tale of two bioorthogonal reactions. Acc Chem Res, 2011, 44( 9): 666– 676

[19] Ghosh A , Fischer P . Controlled propulsion of artificial magnetic nanostructured propellers. Nano Lett, 2009, 9( 6): 2243– 2245

[20] Grammel M , Hang HC . Chemical reporters for biological discovery. Nat Chem Biol, 2013, 9( 8): 475– 484

[21] Gupta A , Das R , Yesilbag Tonga G , Mizuhara T , Rotello VM . Charge-switchable nanozymes for bioorthogonal imaging of biofilm-associated infections. ACS Nano, 2018, 12( 1): 89– 94

[22] Hang HC , Yu C , Kato DL , Bertozzi CR . A metabolic labeling approach toward proteomic analysis of mucin-type O-linked glycosylation. Proc Natl Acad Sci USA, 2003, 100( 25): 14846– 14851

[23] Hoop M , Ribeiro AS , Rösch D , Weinand P , Mendes N , Mushtaq F , Chen X-Z , Shen Y , Pujante CF , Puigmartí-Luis J , Paredes J , Nelson BJ , Pêgo AP , Pané S . Mobile magnetic nanocatalysts for bioorthogonal targeted cancer therapy. Adv Funct Mater, 2018, 28( 25): 1705920

[24] Jeschek M , Reuter R , Heinisch T , Trindler C , Klehr J , Panke S , Ward TR . Directed evolution of artificial metalloenzymes for in vivo metathesis. Nature, 2016, 537( 7622): 661– 665

[25] Ji X , Pan Z , Yu B , De La Cruz LK , Zheng Y , Ke B , Wang B . Click and release: bioorthogonal approaches to "on-demand" activation of prodrugs. Chem Soc Rev, 2019, 48( 4): 1077– 1094

[26] Jiang X , Wang R . Recent developments in catalytic asymmetric inverse-electron-demand Diels–Alder reaction. Chem Rev, 2013, 113( 7): 5515– 5546

[27] Kalluri R , LeBleu VS . The biology, function, and biomedical applications of exosomes. Science, 2020, 367( 6478): eaau6977

[28] Kenry B . Bio-orthogonal click chemistry for in vivo bioimaging. Trends Chem, 2019, 1( 8): 763– 778

[29] Kim J , Bertozzi CR . A bioorthogonal reaction of N-oxide and boron reagents. Angew Chem Int Ed, 2015, 54( 52): 15777– 15781

[30] Lang K , Chin JW . Cellular incorporation of unnatural amino acids and bioorthogonal labeling of proteins. Chem Rev, 2014, 114( 9): 4764– 4806

[31] Laughlin ST , Baskin JM , Amacher SL , Bertozzi CR . In vivo imaging of membrane-associated glycans in developing zebrafish. Science, 2008, 320( 5876): 664– 667

[32] Li B , Liu P , Wu H , Xie X , Chen Z , Zeng F , Wu S . A bioorthogonal nanosystem for imaging and in vivo tumor inhibition. Biomaterials, 2017, 138 : 57– 68

[33] Li J , Chen PR . Development and application of bond cleavage reactions in bioorthogonal chemistry. Nat Chem Biol, 2016, 12( 3): 129– 137

[34] Li Z , Shen D , Hu S , Su T , Huang K , Liu F , Hou L , Cheng K . Pretargeting and bioorthogonal click chemistry-mediated endogenous stem cell homing for heart repair. ACS Nano, 2018, 12( 12): 12193– 12200

[35] Lin YA , Chalker JM , Floyd N , Bernardes GJL , Davis BG . Allyl sulfides are privileged substrates in aqueous cross-metathesis: application to site-selective protein modification. J Am Chem Soc, 2008, 130( 30): 9642– 9643

[36] Ma Y , Wang M , Li W , Zhang Z , Zhang X , Tan T , Zhang XE , Cui Z . Live cell imaging of single genomic loci with quantum dot-labeled TALEs. Nat Commun, 2017, 8 : 15318

[37] Munoz J , Heck AJ . From the human genome to the human proteome. Angew Chem Int Ed, 2014, 53( 41): 10864– 10866

[38] Nagamune T . Biomolecular engineering for nanobio/bionanotechnology. Nano Converg, 2017, 4( 1): 9

[39] Ngo AH , Bose S , Do LH . Intracellular chemistry: integrating molecular inorganic catalysts with living systems. Chemistry, 2018, 24( 42): 10584– 10594

[40] Okamoto Y , Kojima R , Schwizer F , Bartolami E , Heinisch T , Matile S , Fussenegger M , Ward TR . A cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell. Nat Commun, 2018, 9( 1): 1943

[41] Oliveira BL , Guo Z , Bernardes GJL . Inverse electron demand Diels–Alder reactions in chemical biology. Chem Soc Rev, 2017, 46( 16): 4895– 4950

[42] Perez-Lopez AM , Rubio-Ruiz B , Sebastian V , Hamilton L , Adam C , Bray TL , Irusta S , Brennan PM , Lloyd-Jones GC , Sieger D , Santamaria J , Unciti-Broceta A . Gold-triggered uncaging chemistry in living systems. Angew Chem Int Ed, 2017, 56( 41): 12548– 12552

[43] Prescher JA , Bertozzi CR . Chemistry in living systems. Nat Chem Biol, 2005, 1( 1): 13– 21

[44] Prescher JA , Dube DH , Bertozzi CR . Chemical remodelling of cell surfaces in living animals. Nature, 2004, 430( 7002): 873– 877

[45] Ramil CP , Lin Q . Bioorthogonal chemistry: strategies and recent developments. Chem Commun, 2013, 49( 94): 11007– 11022

[46] Rebelein JG , Ward TR . In vivo catalyzed new-to-nature reactions. Curr Opin Biotechnol, 2018, 53 : 106– 114

[47] Ritter C , Nett N , Acevedo-Rocha CG , Lonsdale R , Kraling K , Dempwolff F , Hoebenreich S , Graumann PL , Reetz MT , Meggers E . Bioorthogonal enzymatic activation of caged compounds. Angew Chem Int Ed, 2015, 54( 45): 13440– 13443

[48] Sancho-Albero M , Rubio-Ruiz B , Perez-Lopez AM , Sebastian V , Martin-Duque P , Arruebo M , Santamaria J , Unciti-Broceta A . Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis. Nat Catal, 2019, 2( 10): 864– 872

[49] Sasmal PK , Streu CN , Meggers E . Metal complex catalysis in living biological systems. Chem Commun, 2013, 49( 16): 1581– 1587

[50] Saxon E , Bertozzi CR . Cell surface engineering by a modified Staudinger reaction. Science, 2000, 287( 5460): 2007– 2010

[51] Sletten EM , Bertozzi CR . Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew Chem Int Ed, 2009, 48( 38): 6974– 6998

[52] Soto F , Wang J , Ahmed R , Demirci U . Medical micro/nanorobots in precision medicine. Adv Sci, 2020,

[53] Szponarski M , Schwizer F , Ward TR , Gademann K . On-cell catalysis by surface engineering of live cells with an artificial metalloenzyme. Communs Chem, 2018, 1( 84): 1– 10

[54] Taran F , Porte K , Renoux B , Peraudeau E , Clarhaut J , Eddhif B , Poinot P , Gravel E , Doris E , Wijkhuisen A . Controlled release of micelle payload via sequential enzymatic and bioorthogonal reactions in living systems. Angew Chem Int Ed, 2019, 58( 19): 6366– 6370

[55] Tonga GY , Jeong Y , Duncan B , Mizuhara T , Mout R , Das R , Kim ST , Yeh YC , Yan B , Hou S , Rotello VM . Supramolecular regulation of bioorthogonal catalysis in cells using nanoparticle-embedded transition metal catalysts. Nat Chem, 2015, 7( 7): 597– 603

[56] Unciti-Broceta A . Rise of the nanobots. Nat Chem, 2015, 7( 7): 538– 539

[57] Volker T , Meggers E . Transition-metal-mediated uncaging in living human cells — an emerging alternative to photolabile protecting groups. Curr Opin Chem Biol, 2015, 25 : 48– 54

[58] Vong K, Tanaka K (2020) In vivo metal catalysis in living biological systems. In: Tanaka K and Vong K (eds). Handbook of in vivo chemistry in mice: from lab to living system. Wiley-VCH Verlag GmbH & Co. KgaA, pp309-353. https://doi.org/10.1002/9783527344406.ch11

[59] Wang F , Zhang Y , Du Z , Ren J , Qu X . Designed heterogeneous palladium catalysts for reversible light-controlled bioorthogonal catalysis in living cells. Nat Commun, 2018, 9( 1): 1209

[60] Wang J , Cheng B , Li J , Zhang Z , Hong W , Chen X , Chen PR . Chemical remodeling of cell-surface sialic acids through a palladium-triggered bioorthogonal elimination reaction. Angew Chem Int Ed, 2015, 54( 18): 5364– 5368

[61] Wang X , Liu Y , Fan X , Wang J , Ngai WSC , Zhang H , Li J , Zhang G , Lin J , Chen PR . Copper-triggered bioorthogonal cleavage reactions for reversible protein and cell surface modifications. J Am Chem Soc, 2019, 141( 43): 17133– 17141

[62] Weiss JT , Dawson JC , Fraser C , Rybski W , Torres-Sanchez C , Bradley M , Patton EE , Carragher NO , Unciti-Broceta A . Development and bioorthogonal activation of palladium-labile prodrugs of gemcitabine. J Med Chem, 2014a, 57( 12): 5395– 5404

[63] Weiss JT , Dawson JC , Macleod KG , Rybski W , Fraser C , Torres-Sanchez C , Patton EE , Bradley M , Carragher NO , Unciti-Broceta A . Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach. Nat Commun, 2014b, 5 : 3277

[64] Wu J , Wang X , Wang Q , Lou Z , Li S , Zhu Y , Qin L , Wei H . Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II). Chem Soc Rev, 2019, 48( 4): 1004– 1076

[65] Wu P , Shui W , Carlson BL , Hu N , Rabuka D , Lee J , Bertozzi CR . Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag. Proc Natl Acad Sci USA, 2009, 106( 9): 3000– 3005

[66] Xu L , Raabe M , Zegota MM , Nogueira JCF , Chudasama V , Kuan SL , Weil T . Site-selective protein modification via disulfide rebridging for fast tetrazine/trans-cyclooctene bioconjugation. Org Biomol Chem, 2020, 18( 6): 1140– 1147

[67] Yan T , Li F , Qi S , Tian J , Tian R , Hou J , Luo Q , Dong Z , Xu J , Liu J . Light-responsive vesicles for enantioselective release of chiral drugs prepared from a supra-amphiphilic M-helix. Chem Commun, 2020, 56( 1): 149– 152

[68] Yao QX , Lin F , Fan XY , Wang Y , Liu Y , Liu Z , Jiang X , Chen PR , Gao Y . Synergistic enzymatic and bioorthogonal reactions for selective prodrug activation in living systems. Nat Commun, 2018, 9( 1): 5032

[69] Yarin . Nanofibers, nanofluidics, nanoparticles and nanobots for drug and protein delivery systems. Sci Pharm, 2010, 78( 3): 542– 542

[70] Yusop RM , Unciti-Broceta A , Johansson EM , Sanchez-Martin RM , Bradley M . Palladium-mediated intracellular chemistry. Nat Chem, 2011, 3( 3): 239– 243

[71] Zhang C , Zhou X , Yao T , Tian Z , Zhou D . Precision fluorescent labeling of an adeno-associated virus vector to monitor the viral infection pathway. Biotechnol J, 2018, 13( 4): e1700374

[72] Zhang G , Zheng S , Liu H , Chen PR . Illuminating biological processes through site-specific protein labeling. Chem Soc Rev, 2015, 44( 11): 3405– 3417

[73] Zhang X , Liu Y , Gopalakrishnan S , Castellanos-Garcia L , Li G , Malassine M , Uddin I , Huang R , Luther DC , Vachet RW , Rotello VM . Intracellular activation of bioorthogonal nanozymes through endosomal proteolysis of the protein corona. ACS Nano, 2020, 14( 4): 4767– 4773

[74] Zheng M , Zheng L , Zhang P , Li J , Zhang Y . Development of bioorthogonal reactions and their applications in bioconjugation. Molecules, 2015, 20( 2): 3190– 3205

[75] Zheng Y , Ji X , Yu B , Ji K , Gallo D , Csizmadia E , Zhu M , Choudhury MR , De La Cruz LKC , Chittavong V , Pan Z , Yuan Z , Otterbein LE , Wang B . Enrichment-triggered prodrug activation demonstrated through mitochondria-targeted delivery of doxorubicin and carbon monoxide. Nat Chem, 2018, 10( 7): 787– 794

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (91859101, 81971744, U1932107, 82001952 and 81471786), National Natural Science Foundation of Tianjin (19JCZDJC34000), the Innovation Foundation of Tianjin University, and CAS Interdisciplinary Innovation Team (JCTD-2020-08).

Compliance with ethics guidelines

Conflict of interest Si Sun, Xinzhu Chen, Jing Chen, Junying Wang and Xiao-dong Zhang declare that they have no conflict of interest. Human and animal rights and informed consent This article does not contain any studies with human or animal subjects performed by any of the authors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

RIGHTS & PERMISSIONS

2021 The Author(s) 2021. Published by Higher Education Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0)