Fundamentals and applications of enzyme powered micro/nano-motors

Micro/nanomotors (MNMs) are miniaturized machines that can convert many kinds of energy into mechanical motion. Over the past decades, a variety of driving mechanisms have been developed, which have greatly extended the application scenarios of MNMs. Enzymes exist in natural organisms which can convert chemical energy into mechanical force. It is an innovative attempt to utilize enzymes as biocatalyst providing driving force for MNMs. The fuels for enzymatic reactions are biofriendly as compared to traditional counterparts, which makes enzyme-powered micro/nanomotors (EMNMs) of great value in biomedical field for their nature of biocompatibility. Until now, EMNMs with various shapes can be propelled by catalase, urease and many others. Also, they can be endowed with multiple functionalities to accomplish on-demand tasks. Herein, combined with the development process of EMNMs, we are committed to present a comprehensive understanding of EMNMs, including their types, propelling principles, and potential applications. In this review, we will introduce single enzyme that can be used as motor, enzyme powered molecule motors and other micro/nano-architectures. The fundamental mechanism of energy conversion process of EMNMs and crucial factors that affect their movement behavior will be discussed. The current progress of proof-of-concept applications of EMNMs will also be elaborated in detail. At last, we will summarize and prospect the opportunities and challenges that EMNMs will face in their future development.

[1]  Jie Wu,et al.  Motion of Enzyme-Powered Microshell Motors. , 2019, Chemistry, an Asian journal.

[2]  Juliane Simmchen,et al.  Asymmetric hybrid silica nanomotors for capture and cargo transport: towards a novel motion-based DNA sensor. , 2012, Small.

[3]  Wei Gao,et al.  Self-propelled chemically-powered plant-tissue biomotors. , 2013, Chemical communications.

[4]  Samuel Sánchez,et al.  Bubble-Free Propulsion of Ultrasmall Tubular Nanojets Powered by Biocatalytic Reactions , 2016, Journal of the American Chemical Society.

[5]  Joseph J. Richardson,et al.  Superassembled Biocatalytic Porous Framework Micromotors with Reversible and Sensitive pH‐Speed Regulation at Ultralow Physiological H2O2 Concentration , 2019, Advanced Functional Materials.

[6]  Daeyeon Lee,et al.  Enzymatically Powered Surface-Associated Self-Motile Protocells. , 2018, Small.

[7]  E. J. Loveridge,et al.  Protein motions and dynamic effects in enzyme catalysis. , 2015, Physical chemistry chemical physics : PCCP.

[8]  A. Leshansky,et al.  Highly Efficient Freestyle Magnetic Nanoswimmer. , 2017, Nano letters.

[9]  Samuel Sanchez,et al.  Enzyme‐Powered Nanobots Enhance Anticancer Drug Delivery , 2018 .

[10]  Ronnie H. Fang,et al.  Enzyme-powered Janus platelet cell robots for active and targeted drug delivery , 2020, Science Robotics.

[11]  J. Ross,et al.  Direct Single Molecule Imaging of Enhanced Enzyme Diffusion. , 2018, Physical review letters.

[12]  Fei Wu,et al.  Krebs cycle metabolon formation: metabolite concentration gradient enhanced compartmentation of sequential enzymes. , 2015, Chemical communications.

[13]  Félix Sancenón,et al.  Enzyme-Powered Gated Mesoporous Silica Nanomotors for On-Command Intracellular Payload Delivery. , 2019, ACS nano.

[14]  A. Turberfield,et al.  A free-running DNA motor powered by a nicking enzyme. , 2005, Angewandte Chemie.

[15]  A. Mikhailov,et al.  Nanoscale swimmers: hydrodynamic interactions and propulsion of molecular machines , 2010 .

[16]  Henry Shum,et al.  Harnessing catalytic pumps for directional delivery of microparticles in microchambers , 2017, Nature Communications.

[17]  Fei Peng,et al.  Tadpole-like unimolecular nanomotor with sub-100 nm size swims in a tumor microenvironment model. , 2019, Nano letters.

[18]  Ferran Feixas,et al.  Intrinsic enzymatic properties modulate the self-propulsion of micromotors , 2019, Nature Communications.

[19]  Yang Liu,et al.  High-speed DNA-based rolling motors powered by RNase H , 2015, Nature nanotechnology.

[20]  Sadik Esener,et al.  Acoustic droplet vaporization and propulsion of perfluorocarbon-loaded microbullets for targeted tissue penetration and deformation. , 2012, Angewandte Chemie.

[21]  Shizhe Fu,et al.  Motor-based microprobe powered by bio-assembled catalase for motion detection of DNA. , 2017, Biosensors & bioelectronics.

[22]  Xiaohong Li,et al.  Janus micromotors for motion-capture-ratiometric fluorescence detection of circulating tumor cells , 2020 .

[23]  Ignacio Pagonabarraga,et al.  Self-Propulsion of Active Colloids via Ion Release: Theory and Experiments. , 2020, Physical review letters.

[24]  Martin Pumera,et al.  Catalytic DNA-Functionalized Self-Propelled Micromachines for Environmental Remediation , 2016 .

[25]  Susana Campuzano,et al.  Single Cell Real-Time miRNAs Sensing Based on Nanomotors. , 2015, ACS nano.

[26]  L. Kay,et al.  Intrinsic dynamics of an enzyme underlies catalysis , 2005, Nature.

[27]  T. Tlusty,et al.  Enzyme leaps fuel antichemotaxis , 2017, Proceedings of the National Academy of Sciences.

[28]  Henry Shum,et al.  Solutal and thermal buoyancy effects in self-powered phosphatase micropumps. , 2017, Soft matter.

[29]  Joachim Bill,et al.  Self-Assembled Phage-Based Colloids for High Localized Enzymatic Activity. , 2019, ACS nano.

[30]  M. Gilson,et al.  Substrate-driven chemotactic assembly in an enzyme cascade. , 2018, Nature chemistry.

[31]  H. Hess,et al.  Aldolase Does Not Show Enhanced Diffusion in Dynamic Light Scattering Experiments. , 2018, Nano letters.

[32]  Ayusman Sen,et al.  Chemotactic separation of enzymes. , 2014, ACS nano.

[33]  Carlo D. Montemagno,et al.  Constructing nanomechanical devices powered by biomolecular motors , 1999 .

[34]  Kazuhiko Kinosita,et al.  Direct observation of the rotation of F1-ATPase , 1997, Nature.

[35]  T. Mallouk,et al.  Self-powered enzyme micropumps. , 2014, Nature chemistry.

[36]  G. Battaglia,et al.  Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing , 2016, Science Advances.

[37]  Brigitte Städler,et al.  Double-Fueled Janus Swimmers with Magnetotactic Behavior. , 2017, ACS nano.

[38]  S. Sánchez,et al.  Lipase-Powered Mesoporous Silica Nanomotors for Triglyceride Degradation. , 2019, Angewandte Chemie.

[39]  Xuesi Chen,et al.  A Strategy of Killing Three Birds with One Stone for Cancer Therapy through Regulating Tumor Microenvironment by H2O2-Responsive Gene Delivery System. , 2019, ACS applied materials & interfaces.

[40]  Wei Gao,et al.  Artificial enzyme-powered microfish for water-quality testing. , 2013, ACS nano.

[41]  Jinhong Guo,et al.  Bilayer Tubular Micromotors for Simultaneous Environmental Monitoring and Remediation. , 2018, ACS applied materials & interfaces.

[42]  Masasuke Yoshida,et al.  Mechanically driven ATP synthesis by F1-ATPase , 2004, Nature.

[43]  K N Houk,et al.  Molecular dynamics explorations of active site structure in designed and evolved enzymes. , 2015, Accounts of chemical research.

[44]  Steven M Russell,et al.  Multifunctional motion-to-color janus transducers for the rapid detection of sepsis biomarkers in whole blood. , 2019, Biosensors & bioelectronics.

[45]  R. Golestanian,et al.  Exothermicity Is Not a Necessary Condition for Enhanced Diffusion of Enzymes. , 2017, Nano letters.

[46]  Darrell Velegol,et al.  Positive and negative chemotaxis of enzyme-coated liposome motors , 2019, Nature Nanotechnology.

[47]  Thomas E Mallouk,et al.  Schooling behavior of light-powered autonomous micromotors in water. , 2009, Angewandte Chemie.

[48]  Adam Heller,et al.  Bioelectrochemical propulsion. , 2005, Journal of the American Chemical Society.

[49]  Jiangtao Xu,et al.  Biocatalytic self-propelled submarine-like metal-organic framework microparticles with pH-triggered buoyancy control for directional vertical motion , 2019, Materials Today.

[50]  S. Arai,et al.  Rotation mechanism of Enterococcus hirae V1-ATPase based on asymmetric crystal structures , 2013, Nature.

[51]  P. Boyer,et al.  The binding change mechanism for ATP synthase--some probabilities and possibilities. , 1993, Biochimica et biophysica acta.

[52]  Xing Ma,et al.  Biomedical Micro‐/Nanomotors: From Overcoming Biological Barriers to In Vivo Imaging , 2020, Advanced materials.

[53]  Samudra Sengupta,et al.  Substrate catalysis enhances single-enzyme diffusion. , 2010, Journal of the American Chemical Society.

[54]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[55]  Anita Jannasch,et al.  Self-Sensing Enzyme-Powered Micromotors Equipped with pH-Responsive DNA Nanoswitches. , 2019, Nano letters.

[56]  Paul R Selvin,et al.  Why kinesin is so processive , 2009, Proceedings of the National Academy of Sciences.

[57]  Xiaohong Li,et al.  Enzyme-powered Janus nanomotors launched from intratumoral depots to address drug delivery barriers , 2019, Chemical Engineering Journal.

[58]  Samuel Sanchez,et al.  Bio-catalytic mesoporous Janus nano-motors powered by catalase enzyme , 2017 .

[59]  Kevin Kaufmann,et al.  Nanomotors responsive to nerve-agent vapor plumes. , 2016, Chemical communications.

[60]  Huangxian Ju,et al.  Bubble-Propelled Jellyfish-like Micromotors for DNA Sensing. , 2019, ACS applied materials & interfaces.

[61]  Miss A.O. Penney (b) , 1974, The New Yale Book of Quotations.

[62]  W. Xi,et al.  Rolled-up magnetic microdrillers: towards remotely controlled minimally invasive surgery. , 2013, Nanoscale.

[63]  J. Jansen,et al.  Self‐Propelled PLGA Micromotor with Chemotactic Response to Inflammation , 2020, Advanced healthcare materials.

[64]  D. Velegol,et al.  A Theory of Enzyme Chemotaxis: From Experiments to Modeling. , 2018, Biochemistry.

[65]  Samuel Sánchez,et al.  Targeting 3D Bladder Cancer Spheroids with Urease-Powered Nanomotors. , 2018, ACS nano.

[66]  Kambiz M. Hamadani,et al.  The heat released during catalytic turnover enhances the diffusion of an enzyme , 2014, Nature.

[67]  Masasuke Yoshida,et al.  ATP synthase — a marvellous rotary engine of the cell , 2001, Nature Reviews Molecular Cell Biology.

[68]  M. Futai,et al.  The mechanism of rotating proton pumping ATPases. , 2010, Biochimica et biophysica acta.

[69]  Patrick J. Smith,et al.  Reactive Inkjet Printing of Functional Silk Stirrers for Enhanced Mixing and Sensing. , 2018, Small.

[70]  M. Zacharias,et al.  Subnanometre enzyme mechanics probed by single-molecule force spectroscopy , 2016, Nature Communications.

[71]  D. Velegol,et al.  Motility of Enzyme-Powered Vesicles , 2019, bioRxiv.

[72]  Kayla Gentile,et al.  Powering Motion with Enzymes. , 2018, Accounts of chemical research.

[73]  P. Fischer,et al.  Diffusion Measurements of Swimming Enzymes with Fluorescence Correlation Spectroscopy. , 2018, Accounts of chemical research.

[74]  Ada-Ioana Bunea,et al.  Nanorods with Biocatalytically Induced Self‐Electrophoresis , 2014 .

[75]  Molecular motors: myosins move ahead of the pack. , 2014, Nature nanotechnology.

[76]  D. Wilson,et al.  Stimulus-responsive nanomotors based on gated enzyme-powered Janus Au-mesoporous silica nanoparticles for enhanced cargo delivery. , 2019, Chemical communications.

[77]  Ayusman Sen,et al.  Enhanced Diffusion of Passive Tracers in Active Enzyme Solutions. , 2017, Nano letters.

[78]  Darrell Velegol,et al.  A Theory of Enzyme Chemotaxis: From Experiments to Modeling. , 2018, Biochemistry.

[79]  Samuel Sánchez,et al.  Chemically powered micro- and nanomotors. , 2015, Angewandte Chemie.

[80]  Daniela A Wilson,et al.  Spatial control over catalyst positioning on biodegradable polymeric nanomotors , 2019, Nature Communications.

[81]  Satoshi Nakata,et al.  Periodic Oscillatory Motion of a Self-Propelled Motor Driven by Decomposition of H2 O2 by Catalase. , 2017, Angewandte Chemie.

[82]  Eleanor Stride,et al.  Ultrasound-Propelled Nanocups for Drug Delivery , 2015, Small.

[83]  Loai K. E. A. Abdelmohsen,et al.  Enzyme-driven biodegradable nanomotor based on tubular-shaped polymeric vesicles , 2018 .

[84]  Taylor Courtney,et al.  Enzyme Micropump‐Based Inhibitor Assays , 2016 .

[85]  R. Astumian,et al.  DNA polymerase as a molecular motor and pump. , 2014, ACS nano.

[86]  Allen Pei,et al.  Water-driven micromotors. , 2012, ACS nano.

[87]  Ramin Golestanian,et al.  Mechanical response of a small swimmer driven by conformational transitions. , 2007, Physical review letters.

[88]  Andre Levchenko,et al.  Sub-Cellular Resolution Delivery of a Cytokine via Precisely Manipulated Nanowires , 2010, Nature nanotechnology.

[89]  Jianguo Guan,et al.  Enhanced Propulsion of Urease-Powered Micromotors by Multilayered Assembly of Ureases on Janus Magnetic Microparticles. , 2020, Langmuir : the ACS journal of surfaces and colloids.

[90]  J. Michael Schurr,et al.  A theory of macromolecular chemotaxis. , 2013, The journal of physical chemistry. B.

[91]  Daniela A Wilson,et al.  Enzyme-Powered Nanomotors with Controlled Size for Biomedical Applications , 2019, ACS nano.

[92]  P. Fischer,et al.  Absolute diffusion measurements of active enzyme solutions by NMR. , 2018, The Journal of chemical physics.

[93]  S. Hammes‐Schiffer Impact of enzyme motion on activity. , 2002, Biochemistry.

[94]  Jonathan Howse,et al.  Importance of particle tracking and calculating the mean-squared displacement in distinguishing nanopropulsion from other processes. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[95]  Shizhe Fu,et al.  An efficient enzyme-powered micromotor device fabricated by cyclic alternate hybridization assembly for DNA detection. , 2017, Nanoscale.

[96]  D. Wilson,et al.  High-Throughput Design of Biocompatible Enzyme-Based Hydrogel Microparticles with Autonomous Movement. , 2018, Angewandte Chemie.

[97]  Oliver Lieleg,et al.  Enzymatically active biomimetic micropropellers for the penetration of mucin gels , 2015, Science Advances.

[98]  Ben L Feringa,et al.  Autonomous propulsion of carbon nanotubes powered by a multienzyme ensemble. , 2008, Chemical communications.

[99]  Matthew J Tyska,et al.  The myosin power stroke. , 2002, Cell motility and the cytoskeleton.

[100]  T. Tlusty,et al.  Enhanced diffusion and oligomeric enzyme dissociation. , 2019, Journal of the American Chemical Society.

[101]  Samuel Sánchez,et al.  Motion Control of Urea-Powered Biocompatible Hollow Microcapsules. , 2016, ACS nano.

[102]  Ramin Golestanian,et al.  Anomalous diffusion of symmetric and asymmetric active colloids. , 2009, Physical review letters.

[103]  Xing Ma,et al.  Self-propelled enzymatic nanomotors for enhancing synergetic photodynamic and starvation therapy by self-accelerated cascade reactions , 2019, Applied Materials Today.

[104]  T. Tlusty,et al.  Catalytic enzymes are active matter , 2018, Proceedings of the National Academy of Sciences.

[105]  M. Welte,et al.  Bidirectional Transport along Microtubules , 2004, Current Biology.

[106]  Ramin Golestanian,et al.  Micromotors Powered by Enzyme Catalysis. , 2015, Nano letters.

[107]  Tsuyoshi Murata,et al.  {m , 1934, ACML.

[108]  Joseph Wang,et al.  Dual-enzyme natural motors incorporating decontamination and propulsion capabilities , 2014 .

[109]  T. Komatsu,et al.  Nonbubble-Propelled Biodegradable Microtube Motors Consisting Only of Protein. , 2019, Chemistry, an Asian journal.

[110]  Tristan Tabouillot,et al.  Enzyme molecules as nanomotors. , 2013, Journal of the American Chemical Society.

[111]  Brigitte Städler,et al.  Enhanced Diffusion of Glucose-Fueled Janus Particles , 2015 .

[112]  A. Mikhailov,et al.  Hydrodynamic collective effects of active protein machines in solution and lipid bilayers , 2015, Proceedings of the National Academy of Sciences.

[113]  Stephen Mann,et al.  Enzyme-powered motility in buoyant organoclay/DNA protocells , 2018, Nature Chemistry.

[114]  Anita Jannasch,et al.  Influence of Enzyme Quantity and Distribution on the Self-Propulsion of Non-Janus Urease-Powered Micromotors. , 2018, Journal of the American Chemical Society.

[115]  Samuel Sánchez,et al.  Fundamental Aspects of Enzyme-Powered Micro- and Nanoswimmers. , 2018, Accounts of chemical research.

[116]  Samuel Sanchez,et al.  Dynamics of biocatalytic microengines mediated by variable friction control. , 2010, Journal of the American Chemical Society.

[117]  R. Golestanian,et al.  Phoresis and Enhanced Diffusion Compete in Enzyme Chemotaxis. , 2018, Nano letters.

[118]  Mingcheng Yang,et al.  Surface Wettability-Directed Propulsion of Glucose-Powered Nanoflask Motors. , 2019, ACS nano.

[119]  H. Noji,et al.  The Rotary Enzyme of the Cell: The Rotation of F1-ATPase , 1998, Science.

[120]  Marlies Nijemeisland,et al.  Dynamic Loading and Unloading of Proteins in Polymeric Stomatocytes: Formation of an Enzyme-Loaded Supramolecular Nanomotor. , 2016, ACS nano.

[121]  Li Zhang,et al.  Artificial bacterial flagella for remote-controlled targeted single-cell drug delivery. , 2014, Small.

[122]  Ramin Golestanian,et al.  Propulsion of a molecular machine by asymmetric distribution of reaction products. , 2005, Physical review letters.

[123]  Henry Shum,et al.  Convective flow reversal in self-powered enzyme micropumps , 2015, Proceedings of the National Academy of Sciences.

[124]  Ada-Ioana Bunea,et al.  Sensing based on the motion of enzyme-modified nanorods. , 2015, Biosensors & bioelectronics.

[125]  Qiang He,et al.  Self-propelled polymer multilayer Janus capsules for effective drug delivery and light-triggered release. , 2014, ACS applied materials & interfaces.

[126]  Xing Ma,et al.  Enzymatic Micromotors as a Mobile Photosensitizer Platform for Highly Efficient On‐Chip Targeted Antibacteria Photodynamic Therapy , 2019, Advanced Functional Materials.

[127]  Zhiguang Wu,et al.  Biodegradable protein-based rockets for drug transportation and light-triggered release. , 2015, ACS applied materials & interfaces.

[128]  Modification with hemeproteins increases the diffusive movement of nanorods in dilute hydrogen peroxide solutions. , 2013, Chemical communications.

[129]  J. Lahann,et al.  Microscale Rockets and Picoliter Containers Engineered from Electrospun Polymeric Microtubes. , 2016, Small.

[130]  Samuel Sanchez,et al.  Enzyme-Powered Hollow Mesoporous Janus Nanomotors. , 2015, Nano letters (Print).