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by Keyword: Propulsion

Chen, SQ, Prado-Morales, C, Sánchez-deAlcázar, D, Sánchez, S, (2024). Enzymatic micro/nanomotors in biomedicine: from single motors to swarms Journal Of Materials Chemistry b 12,

Micro/nanomotors (MNMs) have evolved from single self-propelled entities to versatile systems capable of performing one or multiple biomedical tasks. When single MNMs self-assemble into coordinated swarms, either under external control or triggered by chemical reactions, they offer advantages that individual MNMs cannot achieve. These benefits include intelligent multitasking and adaptability to changes in the surrounding environment. Here, we provide our perspective on the evolution of MNMs, beginning with the development of enzymatic MNMs since the first theoretical model was proposed in 2005. These enzymatic MNMs hold immense promise in biomedicine due to their advantages in biocompatibility and fuel availability. Subsequently, we introduce the design and application of single motors in biomedicine, followed by the control of MNM swarms and their biomedical applications. In the end, we propose viable solutions for advancing the development of MNM swarms and anticipate valuable insights into the creation of more intelligent and controllable MNM swarms for biomedical applications.; Micro/nanomotor swarms propelled by diverse mechanisms.

JTD Keywords: Active particles, Actuation, Behaviors, Biocompatibility, Biomedical applications, Coordination reactions, Design and application, Diffusion, External control, Medical applications, Micromotors, Motion, Nanomotors, Powered nanomotors, Propulsion, Self-assemble, Surrounding environment, Theoretical modeling, Versatile system, Viable solutions


Magdanz, V, Klingner, A, Abelmann, L, Khalil, ISM, (2023). IRONSperm swimming by rigid-body rotation versus transverse bending waves influenced by cell membrane charge Journal Of Micro-Bio Robotics 18, 49-60

Cell membrane potential affects the electrostatic self-assembly of magnetizable nanoparticles around the flagellum of sperm cells, leading to the formation of biohybrid microrobots (i.e., IRONSperm) with various bending stiffness. Here we explain the influence of bull sperm cell membrane potential on the formation of two types of IRONSperm samples that are produced by electrostatic self-assembly. The first type is a proximal-coated soft body with nanoparticles concentrated on the head to maintain high flexibility of the flagellum and create a passively propagating transverse bending wave under the influence of an external rotating magnetic field. The second type is a rigid-body with nanoparticles approximately uniformly distributed along the length to provide arbitrary geometry that maintains a constant chiral shape and propel by rotation about its long axis. We present a magneto-elastohydrodynamic model to predict the swimming speed at low Reynolds number for rigid IRONSperm with arbitrary shapes, and show that decreasing the bending stiffness allows the model to capture the behavior of its soft counterpart. While the response of a rigid chiral IRONSperm is distinguished by a greater swimming speed with a smooth decay with frequency, the benefit of a soft flagellum in certain scenarios would present a much smaller range of frequencies for wireless actuation.

JTD Keywords: Biohybrid, Magnetic, Microrobots, Nanoparticles, Propulsion, Sperm cells


Zhang, KX, Klingner, A, Le Gars, Y, Misra, S, Magdanz, V, Khalil, ISM, (2023). Locomotion of bovine spermatozoa during the transition from individual cells to bundles Proceedings Of The National Academy Of Sciences Of The United States Of America 120, e2211911120

Various locomotion strategies employed by microorganisms are observed in complex biological environments. Spermatozoa assemble into bundles to improve their swimming efficiency compared to individual cells. However, the dynamic mechanisms for the formation of sperm bundles have not been fully characterized. In this study, we numerically and experimentally investigate the locomotion of spermatozoa during the transition from individual cells to bundles of two cells. Three consecutive dynamic behaviors are found across the course of the transition: hydrodynamic attraction/repulsion, alignment, and synchronization. The hydrodynamic attraction/repulsion depends on the relative orientation and distance between spermatozoa as well as their flagellar wave patterns and phase shift. Once the heads are attached, we find a stable equilibrium of the rotational hydrodynamics resulting in the alignment of the heads. The synchronization results from the combined influence of hydrodynamic and mechanical cell-to-cell interactions. Additionally, we find that the flagellar beat is regulated by the interactions during the bundle formation, whereby spermatozoa can synchronize their beats to enhance their swimming velocity.

JTD Keywords: behavior, cilia, collective locomotion, collective motion, competition, flagellar propulsion, hydrodynamics, motility, propulsion, sperm cooperation, tracking, Collective locomotion, Flagellar propulsion, Flagellar synchronization, Spermatozoa bundle


Wang, ZH, Klingner, A, Magdanz, V, Hoppenreijs, MW, Misra, S, Khalil, ISM, (2023). Flagellar Propulsion of Sperm Cells Against a Time-Periodic Interaction Force Advanced Biology 7, e2200210

Sperm cells undergo complex interactions with external environments, such as a solid-boundary, fluid flow, as well as other cells before arriving at the fertilization site. The interaction with the oviductal epithelium, as a site of sperm storage, is one type of cell-to-cell interaction that serves as a selection mechanism. Abnormal sperm cells with poor swimming performance, the major cause of male infertility, are filtered out by this selection mechanism. In this study, collinear bundles, consisting of two sperm cells, generate propulsive thrusts along opposite directions and allow to observe the influence of cell-to-cell interaction on flagellar wave-patterns. The developed elasto-hydrodynamic model demonstrates that steric and adhesive forces lead to highly symmetrical wave-pattern and reduce the bending amplitude of the propagating wave. It is measured that the free cells exhibit a mean flagellar curvature of 6.4 +/- 3.5 rad mm(-1) and a bending amplitude of 13.8 +/- 2.8 rad mm(-1). After forming the collinear bundle, the mean flagellar curvature and bending amplitude are decreased to 1.8 +/- 1.1 and 9.6 +/- 1.4 rad mm(-1), respectively. This study presents consistent theoretical and experimental results important for understanding the adaptive behavior of sperm cells to the external time-periodic force encountered during sperm-egg interaction.

JTD Keywords: bovine sperm cells, cell-to-cell interaction, flagellar propulsion, Bovine sperm cells, Cell-to-cell interaction, Cilia, Filaments, Flagellar propulsion, Hydrodynamic models, Mechanism, Micro-video, Model, Motility, Thermotaxis, Transformations, Transition


Wang, L, Huang, Y, Xu, H, Chen, S, Chen, H, Lin, Y, Wang, X, Liu, X, Sanchez, S, Huang, X, (2022). Contaminants-fueled laccase-powered Fe3O4@SiO2 nanomotors for synergistical degradation of multiple pollutants Materials Today Chemistry 26, 101059

Although an increasing number of micro/nanomotors have been designed for environmental remediation in the past decade, the construction of contaminants-fueled nanomotors for synergistically degrading multiple pollutants simultaneously remains a challenge. Herein, laccase-powered Fe3O4@silica nanomotors are fabricated, assisted with lipase enzyme for the enhanced degradation of multiple contaminants using the contaminants themselves as fuels. Notably, we demonstrate that representative industrial phenols and polycyclic aromatic pollutants possess the ability of triggering the enhanced Brownian motion of laccase nanomotors (De of 1.16 mu m(2)/s in 220 mu M biphenol A (BPA), 1.40 mu m(2)/s in 375 mu M Congo red (CR)). Additionally, the k(cat) value of lipase-assisted laccase-powered nanomotors increased over 1.4 times, enhancing their Brownian motion, while leading to the efficient degradation of multiple contaminants such as BPA, CR, and triacetin droplets within 40 min, simultaneously. Ultimately, the lipase-assisted laccase nanomotors exhibit great advantages over free laccase, free lipase, lipase nanomotors, or laccase nanomotors in K-m, k(cat), catalytic stability, recycling property, and the degradation efficiency of contaminants. Therefore, our work further broadens the library of enzyme-powered nanomotors and provides deep insights in synergistical enzymatic catalysis, thus paving avenues for environmental remediation based on enzyme-powered micro/nanomotors. (C) 2022 Elsevier Ltd. All rights reserved.

JTD Keywords: core, dye, environmental remediation, enzyme catalysis, hybrid, light, microspheres, motors, pollutants removal, propulsion, removal, self-propulsion, shell, Core, Dye, Environmental remediation, Enzyme catalysis, Hybrid, Light, Micro/nanomotors, Micromotors, Microspheres, Motors, Pollutants removal, Propulsion, Removal, Self-propulsion, Shell


Middelhoek, KINA, Magdanz, V, Abelmann, L, Khalil, ISM, (2022). Drug-Loaded IRONSperm clusters: modeling, wireless actuation, and ultrasound imaging Biomedical Materials 17, 65001

Individual biohybrid microrobots have the potential to perform biomedical in vivo tasks such as remote-controlled drug and cell delivery and minimally invasive surgery. This work demonstrates the formation of biohybrid sperm-templated clusters under the influence of an external magnetic field and essential functionalities for wireless actuation and drug delivery. Ferromagnetic nanoparticles are electrostatically assembled around dead sperm cells, and the resulting nanoparticle-coated cells are magnetically assembled into three-dimensional biohybrid clusters. The aim of this clustering is threefold: First, to enable rolling locomotion on a nearby solid boundary using a rotating magnetic field; second, to allow for noninvasive localization; third, to load the cells inside the cluster with drugs for targeted therapy. A magneto-hydrodynamic model captures the rotational response of the clusters in a viscous fluid, and predicts an upper bound for their step-out frequency, which is independent of their volume or aspect ratio. Below the step-out frequency, the rolling velocity of the clusters increases nonlinearly with their perimeter and actuation frequency. During rolling locomotion, the clusters are localized using ultrasound images at a relatively large distance, which makes these biohybrid clusters promising for deep-tissue applications. Finally, we show that the estimated drug load scales with the number of cells in the cluster and can be retained for more than 10 h. The aggregation of microrobots enables them to collectively roll in a predictable way in response to an external rotating magnetic field, and enhances ultrasound detectability and drug loading capacity compared to the individual microrobots. The favorable features of biohybrid microrobot clusters place emphasis on the importance of the investigation and development of collective microrobots and their potential for in vivo applications.

JTD Keywords: drug delivery, magnetic actuation, microrobot aggregation, sperm, Driven, Drug delivery, Magnetic actuation, Magnetotactic bacteria, Microrobot aggregation, Microrobots, Motion, Movement, Propulsion, Sperm, Sphere, Ultrasound, Wall


Arque, X, Patino, T, Sanchez, S, (2022). Enzyme-powered micro- and nano-motors: key parameters for an application-oriented design Chemical Science 13, 9128-9146

Nature has inspired the creation of artificial micro- and nanomotors that self-propel converting chemical energy into mechanical action. These tiny machines have appeared as promising biomedical tools for treatment and diagnosis and have also been used for environmental, antimicrobial or sensing applications. Among the possible catalytic engines, enzymes have emerged as an alternative to inorganic catalysts due to their biocompatibility and the variety and bioavailability of fuels. Although the field of enzyme-powered micro- and nano-motors has a trajectory of more than a decade, a comprehensive framework on how to rationally design, control and optimize their motion is still missing. With this purpose, herein we performed a thorough bibliographic study on the key parameters governing the propulsion of these enzyme-powered devices, namely the chassis shape, the material composition, the motor size, the enzyme type, the method used to incorporate enzymes, the distribution of the product released, the motion mechanism, the motion media and the technique used for motion detection. In conclusion, from the library of options that each parameter offers there needs to be a rational selection and intelligent design of enzymatic motors based on the specific application envisioned.

JTD Keywords: Catalase, Hydrogen-peroxide, Micro/nanomotors, Micromotors, Movement, Nanomotors, Propulsion, Surfactants, Therapy, Tumor microenvironment


Arque, X, Torres, MDT, Patino, T, Boaro, A, Sanchez, S, de la Fuente-Nunez, C, (2022). Autonomous Treatment of Bacterial Infections in Vivo Using Antimicrobial Micro- and Nanomotors Acs Nano 16, 7547-7558

The increasing resistance of bacteria to existing antibiotics constitutes a major public health threat globally. Most current antibiotic treatments are hindered by poor delivery to the infection site, leading to undesired off-target effects and drug resistance development and spread. Here, we describe micro- and nanomotors that effectively and autonomously deliver antibiotic payloads to the target area. The active motion and antimicrobial activity of the silica-based robots are driven by catalysis of the enzyme urease and antimicrobial peptides, respectively. These antimicrobial motors show micromolar bactericidal activity in vitro against different Gram-positive and Gram-negative pathogenic bacterial strains and act by rapidly depolarizing their membrane. Finally, they demonstrated autonomous anti-infective efficacy in vivo in a clinically relevant abscess infection mouse model. In summary, our motors combine navigation, catalytic conversion, and bactericidal capacity to deliver antimicrobial payloads to specific infection sites. This technology represents a much-needed tool to direct therapeutics to their target to help combat drug-resistant infections.

JTD Keywords: antibiotic-resistance, antimicrobial peptides, autonomous treatment, bacterial infection, delivery, ll-37, nanomotors, nanoparticles, peptide, self-propulsion, tissue, vitro, wasp venom, Antibiotic-resistance, Antimicrobial peptides, Autonomous treatment, Bacterial infection, Delivery, Ll-37, Mesoporous silica nanoparticles, Nanomotors, Nanoparticles, Peptide, Self-propulsion, Tissue, Vitro, Wasp venom


Valles, M, Pujals, S, Albertazzi, L, Sánchez, S, (2022). Enzyme Purification Improves the Enzyme Loading, Self-Propulsion, and Endurance Performance of Micromotors Acs Nano 16, 5615-5626

Enzyme-powered micro- and nanomotors make use of biocatalysis to self-propel in aqueous media and hold immense promise for active and targeted drug delivery. Most (if not all) of these micro- and nanomotors described to date are fabricated using a commercially available enzyme, despite claims that some commercial preparations may not have a sufficiently high degree of purity for downstream applications. In this study, the purity of a commercial urease, an enzyme frequently used to power the motion of micro- and nanomotors, was evaluated and found to be impure. After separating the hexameric urease from the protein impurities by size-exclusion chromatography, the hexameric urease was subsequently characterized and used to functionalize hollow silica microcapsules. Micromotors loaded with purified urease were found to be 2.5 times more motile than the same micromotors loaded with unpurified urease, reaching average speeds of 5.5 ?m/s. After comparing a number of parameters, such as enzyme distribution, protein loading, and motor reusability, between micromotors functionalized with purified vs unpurified urease, it was concluded that protein purification was essential for optimal performance of the enzyme-powered micromotor.

JTD Keywords: canavalin, catalysis, delivery, dls, enhanced diffusion, enzyme, lipase immobilization, micromotors, self-propulsion, super-resolution microscopy, urease, Mesoporous silica nanoparticles, Micromotors, Super-resolution microscopy


Dias, JMS, Estima, D, Punte, H, Klingner, A, Marques, L, Magdanz, V, Khalil, ISM, (2022). Modeling and Characterization of the Passive Bending Stiffness of Nanoparticle-Coated Sperm Cells using Magnetic Excitation Advanced Theory And Simulations 5, 2100438

Of all the various locomotion strategies in low- (Formula presented.), traveling-wave propulsion methods with an elastic tail are preferred because they can be developed using simple designs and fabrication procedures. The only intrinsic property of the elastic tail that governs the form and rate of wave propagation along its length is the bending stiffness. Such traveling wave motion is performed by spermatozoa, which possess a tail that is characterized by intrinsic variable stiffness along its length. In this paper, the passive bending stiffness of the magnetic nanoparticle-coated flagella of bull sperm cells is measured using a contactless electromagnetic-based excitation method. Numerical elasto-hydrodynamic models are first developed to predict the magnetic excitation and relaxation of nanoparticle-coated nonuniform flagella. Then solutions are provided for various groups of nonuniform flagella with disparate nanoparticle coatings that relate their bending stiffness to their decay rate after the magnetic field is removed and the flagellum restores its original configuration. The numerical models are verified experimentally, and capture the effect of the nanoparticle coating on the bending stiffness. It is also shown that electrostatic self-assembly enables arbitrarily magnetizable cellular segments with variable stiffness along the flagellum. The bending stiffness is found to depend on the number and location of the magnetized cellular segments. © 2022 The Authors. Advanced Theory and Simulations published by Wiley-VCH GmbH.

JTD Keywords: cilia, flagella, flagellar propulsion, low reynolds numbers, magnetic, microswimmers, passive, sperm cell, Bending stiffness, Cells, Cellulars, Coatings, Decay (organic), Electric excitation, Excited states, Flagellar propulsion, Locomotion strategies, Low reynolds numbers, Magnetic, Magnetic excitations, Nanoparticle coatings, Passive, Propulsion methods, Self assembly, Simple++, Sperm cell, Sperm cells, Stiffness, Travelling waves, Variable stiffness, Wave propagation, Younǵs modulus


Vilela, D, Blanco-Cabra, N, Eguskiza, A, Hortelao, AC, Torrents, E, Sanchez, S, (2021). Drug-Free Enzyme-Based Bactericidal Nanomotors against Pathogenic Bacteria Acs Applied Materials & Interfaces 13, 14964-14973

The low efficacy of current conventional treatments for bacterial infections increases mortality rates worldwide. To alleviate this global health problem, we propose drug-free enzyme-based nanomotors for the treatment of bacterial urinary-tract infections. We develop nanomotors consisting of mesoporous silica nanoparticles (MSNPs) that were functionalized with either urease (U-MSNPs), lysozyme (L-MSNPs), or urease and lysozyme (M-MSNPs), and use them against nonpathogenic planktonic Escherichia coli. U-MSNPs exhibited the highest bactericidal activity due to biocatalysis of urea into NaHCO3 and NH3, which also propels U-MSNPs. In addition, U-MSNPs in concentrations above 200 μg/mL were capable of successfully reducing 60% of the biofilm biomass of a uropathogenic E. coli strain. This study thus provides a proof-of-concept, demonstrating that enzyme-based nanomotors are capable of fighting infectious diseases. This approach could potentially be extended to other kinds of diseases by selecting appropriate biomolecules.

JTD Keywords: biofilms, carbonate, e. coli, enzymatic nanomotors, infections, lysozyme, micromotors, nanomachines, proteins, self-propulsion, Biofilms, E. coli, Eliminate escherichia-coli, Enzymatic nanomotors, Infections, Nanomachines, Self-propulsion


Magdanz, V, Vivaldi, J, Mohanty, S, Klingner, A, Vendittelli, M, Simmchen, J, Misra, S, Khalil, ISM, (2021). Impact of Segmented Magnetization on the Flagellar Propulsion of Sperm-Templated Microrobots Advanced Science 8, 2004037

© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH Technical design features for improving the way a passive elastic filament produces propulsive thrust can be understood by analyzing the deformation of sperm-templated microrobots with segmented magnetization. Magnetic nanoparticles are electrostatically self-assembled on bovine sperm cells with nonuniform surface charge, producing different categories of sperm-templated microrobots. Depending on the amount and location of the nanoparticles on each cellular segment, magnetoelastic and viscous forces determine the wave pattern of each category during flagellar motion. Passively propagating waves are induced along the length of these microrobots using external rotating magnetic fields and the resultant wave patterns are measured. The response of the microrobots to the external field reveals distinct flow fields, propulsive thrust, and frequency responses during flagellar propulsion. This work allows predictions for optimizing the design and propulsion of flexible magnetic microrobots with segmented magnetization.

JTD Keywords: biohybrid microrobots, flagellar propulsion, magnetic actuation, nanoparticles, sperm cells, Biohybrid microrobots, Flagellar propulsion, Magnetic actuation, Nanoparticles, Sperm cells


Ebrahimi, N, Bi, CH, Cappelleri, DJ, Ciuti, G, Conn, AT, Faivre, D, Habibi, N, Hosovsky, A, Iacovacci, V, Khalil, ISM, Magdanz, V, Misra, S, Pawashe, C, Rashidifar, R, Soto-Rodriguez, PED, Fekete, Z, Jafari, A, (2021). Magnetic Actuation Methods in Bio/Soft Robotics Advanced Functional Materials 31, 2005137

© 2020 Wiley-VCH GmbH In recent years, magnetism has gained an enormous amount of interest among researchers for actuating different sizes and types of bio/soft robots, which can be via an electromagnetic-coil system, or a system of moving permanent magnets. Different actuation strategies are used in robots with magnetic actuation having a number of advantages in possible realization of microscale robots such as bioinspired microrobots, tetherless microrobots, cellular microrobots, or even normal size soft robots such as electromagnetic soft robots and medical robots. This review provides a summary of recent research in magnetically actuated bio/soft robots, discussing fabrication processes and actuation methods together with relevant applications in biomedical area and discusses future prospects of this way of actuation for possible improvements in performance of different types of bio/soft robots.

JTD Keywords: capsule endoscope, controlled propulsion, conventional gastroscopy, digital microfluidics, guided capsule, liquid-metal, magnetic drug delivery, magnetic microrobots, magnetically guided capsule endoscopy, magnetotactic bacteria, nanoscribe ip-dip, navigation system, Gallium-indium egain, Magnetic bioinspired micromanipulation, Magnetic drug delivery, Magnetic microrobots, Magnetically guided capsule endoscopy, Magnetotactic bacteria


Mestre, R, Cadefau, N, Hortelao, AC, Grzelak, J, Gich, M, Roig, A, Sánchez, S, (2021). Nanorods Based on Mesoporous Silica Containing Iron Oxide Nanoparticles as Catalytic Nanomotors: Study of Motion Dynamics Chemnanomat 7, 134-140

© 2020 Wiley-VCH GmbH Self-propelled particles and, in particular, those based on mesoporous silica, have raised considerable interest due to their potential applications in the environmental and biomedical fields thanks to their biocompatibility, tunable surface chemistry and large porosity. Although spherical particles have been widely used to fabricate nano- and micromotors, not much attention has been paid to other geometries, such as nanorods. Here, we report the fabrication of self-propelled mesoporous silica nanorods (MSNRs) that move by the catalytic decomposition of hydrogen peroxide by a sputtered Pt layer, Fe2O3 nanoparticles grown within the mesopores, or the synergistic combination of both. We show that motion can occur in two distinct sub-populations characterized by two different motion dynamics, namely enhanced diffusion or directional propulsion, especially when both catalysts are used. These results open up the possibility of using MSNRs as chassis for the fabrication of self-propelled particles for the environmental or biomedical fields.

JTD Keywords: Mesoporous silica, Nanomotors, Nanorods, Porous materials, Self-propulsion


Mestre, R., Cadefau, N., Hortelão, A. C., Grzelak, J., Gich, M., Roig, A., Sánchez, S., (2020). Nanorods based on mesoporous silica containing iron oxide nanoparticles as catalytic nanomotors: Study of motion dynamics ChemNanoMat 7, (2), 134-140

Self-propelled particles and, in particular, those based on mesoporous silica, have raised considerable interest due to their potential applications in the environmental and biomedical fields thanks to their biocompatibility, tunable surface chemistry and large porosity. Although spherical particles have been widely used to fabricate nano- and micromotors, not much attention has been paid to other geometries, such as nanorods. Here, we report the fabrication of self-propelled mesoporous silica nanorods (MSNRs) that move by the catalytic decomposition of hydrogen peroxide by a sputtered Pt layer, Fe2O3 nanoparticles grown within the mesopores, or the synergistic combination of both. We show that motion can occur in two distinct sub-populations characterized by two different motion dynamics, namely enhanced diffusion or directional propulsion, especially when both catalysts are used. These results open up the possibility of using MSNRs as chassis for the fabrication of self-propelled particles for the environmental or biomedical fields

JTD Keywords: Mesoporous silica, Nanomotors, Nanorods, Porous materials, Self-propulsion


Xu, D., Wang, Y., Liang, C., You, Y., Sanchez, S., Ma, X., (2020). Self-propelled micro/nanomotors for on-demand biomedical cargo transportation Small 16, (27), 1902464

Micro/nanomotors (MNMs) are miniaturized machines that can perform assigned tasks at the micro/nanoscale. Over the past decade, significant progress has been made in the design, preparation, and applications of MNMs that are powered by converting different sources of energy into mechanical force, to realize active movement and fulfill on-demand tasks. MNMs can be navigated to desired locations with precise controllability based on different guidance mechanisms. A considerable research effort has gone into demonstrating that MNMs possess the potential of biomedical cargo loading, transportation, and targeted release to achieve therapeutic functions. Herein, the recent advances of self-propelled MNMs for on-demand biomedical cargo transportation, including their self-propulsion mechanisms, guidance strategies, as well as proof-of-concept studies for biological applications are presented. In addition, some of the major challenges and possible opportunities of MNMs are identified for future biomedical applications in the hope that it may inspire future research.

JTD Keywords: Biomedical applications, Cargo transportation, Guidance strategies, Micro/nanomotors, Self-propulsion


Hortelão, Ana C., Carrascosa, Rafael, Murillo-Cremaes, Nerea, Patiño, Tania, Sánchez, Samuel, (2019). Targeting 3D bladder cancer spheroids with urease-powered nanomotors ACS Nano 13, (1), 429-439

Cancer is one of the main causes of death around the world, lacking efficient clinical treatments that generally present severe side effects. In recent years, various nanosystems have been explored to specifically target tumor tissues, enhancing the efficacy of cancer treatment and minimizing the side effects. In particular, bladder cancer is the ninth most common cancer worldwide and presents a high survival rate but serious recurrence levels, demanding an improvement in the existent therapies. Here, we present urease-powered nanomotors based on mesoporous silica nanoparticles that contain both polyethylene glycol and anti-FGFR3 antibody on their outer surface to target bladder cancer cells in the form of 3D spheroids. The autonomous motion is promoted by urea, which acts as fuel and is inherently present at high concentrations in the bladder. Antibody-modified nanomotors were able to swim in both simulated and real urine, showing a substrate-dependent enhanced diffusion. The internalization efficiency of the antibody-modified nanomotors into the spheroids in the presence of urea was significantly higher compared with antibody-modified passive particles or bare nanomotors. Furthermore, targeted nanomotors resulted in a higher suppression of spheroid proliferation compared with bare nanomotors, which could arise from the local ammonia production and the therapeutic effect of anti-FGFR3. These results hold significant potential for the development of improved targeted cancer therapy and diagnostics using biocompatible nanomotors.

JTD Keywords: 3D cell culture, Bladder cancer, Enzymatic catalysis, Nanomachines, Nanomotors, Self-propulsion, Targeting


Wang, Lei, Hortelão, Ana C., Huang, Xin, Sánchez, Samuel, (2019). Lipase-powered mesoporous silica nanomotors for triglyceride degradation Angewandte Chemie International Edition 58, (24), 7992-7996

We report lipase-based nanomotors that are capable of enhanced Brownian motion over long periods of time in triglyceride solution and of degrading triglyceride droplets that mimic “blood lipids”. We achieved about 40 min of enhanced diffusion of lipase-modified mesoporous silica nanoparticles (MSNPs) through a biocatalytic reaction between lipase and its corresponding water-soluble oil substrate (triacetin) as fuel, which resulted in an enhanced diffusion coefficient (ca. 50 % increase) at low triacetin concentration (<10 mm). Lipase not only serves as the power engine but also as a highly efficient cleaner for the triglyceride droplets (e.g., tributyrin) in PBS solution, which could yield potential biomedical applications, for example, for dealing with diseases related to the accumulation of triglycerides, or for environmental remediation, for example, for the degradation of oil spills.

JTD Keywords: Enzyme nanomotors, Lipase, Micromotors, Oil removal, Self-propulsion


Patiño, Tania, Porchetta, Alessandro, Jannasch, Anita, Lladó, Anna, Stumpp, Tom, Schäffer, Erik, Ricci, Francesco, Sánchez, Samuel, (2019). Self-sensing enzyme-powered micromotors equipped with pH-responsive DNA nanoswitches Nano Letters 19, (6), 3440-3447

Biocatalytic micro- and nanomotors have emerged as a new class of active matter self-propelled through enzymatic reactions. The incorporation of functional nanotools could enable the rational design of multifunctional micromotors for simultaneous real-time monitoring of their environment and activity. Herein, we report the combination of DNA nanotechnology and urease-powered micromotors as multifunctional tools able to swim, simultaneously sense the pH of their surrounding environment, and monitor their intrinsic activity. With this purpose, a FRET-labeled triplex DNA nanoswitch for pH sensing was immobilized onto the surface of mesoporous silica-based micromotors. During self-propulsion, urea decomposition and the subsequent release of ammonia led to a fast pH increase, which was detected by real-time monitoring of the FRET efficiency through confocal laser scanning microscopy at different time points (i.e., 30 s, 2 and 10 min). Furthermore, the analysis of speed, enzymatic activity, and propulsive force displayed a similar exponential decay, matching the trend observed for the FRET efficiency. These results illustrate the potential of using specific DNA nanoswitches not only for sensing the micromotors’ surrounding microenvironment but also as an indicator of the micromotor activity status, which may aid to the understanding of their performance in different media and in different applications.

JTD Keywords: Micromotors, DNA-nanoswitch, pH detection, Self-propulsion, Nanosensors, Nanomotors


Katuri, Jaideep, Caballero, David, Voituriez, R., Samitier, Josep, Sanchez, Samuel, (2018). Directed flow of micromotors through alignment interactions with micropatterned ratchets ACS Nano 12, (7), 7282-7291

To achieve control over naturally diffusive, out-of-equilibrium systems composed of self-propelled particles, such as cells or self-phoretic colloids, is a long-standing challenge in active matter physics. The inherently random motion of these active particles can be rectified in the presence of local and periodic asymmetric cues given that a non-trivial interaction exists between the self-propelled particle and the cues. Here, we exploit the phoretic and hydrodynamic interactions of synthetic micromotors with local topographical features to break the time-reversal symmetry of particle trajectories and to direct a macroscopic flow of micromotors. We show that the orientational alignment induced on the micromotors by the topographical features, together with their geometrical asymmetry, are crucial in generating directional particle flow. We also show that our system can be used to concentrate micromotors in confined spaces and identify the interactions responsible for this effect. Finally, we develop a minimal model which identifies the main parameters of the system responsible for the observed rectification. Overall, our system allows for robust control over both temporal and spatial distribution of synthetic micromotors.

JTD Keywords: Active colloids, Directional control, Janus particles, Micromotors, Self-propulsion


Vilela, D., Stanton, M. M., Parmar, J., Sánchez, S., (2017). Microbots decorated with silver nanoparticles kill bacteria in aqueous media ACS Applied Materials & Interfaces 9, (27), 22093-22100

Water contamination is one of the most persistent problems of public health. Resistance of some pathogens to conventional disinfectants can require the combination of multiple disinfectants or increased disinfectant doses, which may produce harmful byproducts. Here, we describe an efficient method for disinfecting Escherichia coli and removing the bacteria from contaminated water using water self-propelled Janus microbots decorated with silver nanoparticles (AgNPs). The structure of a spherical Janus microbot consists of a magnesium (Mg) microparticle as a template that also functions as propulsion source by producing hydrogen bubbles when in contact with water, an inner iron (Fe) magnetic layer for their remote guidance and collection, and an outer AgNP-coated gold (Au) layer for bacterial adhesion and improving bactericidal properties. The active motion of microbots increases the chances of the contact of AgNPs on the microbot surface with bacteria, which provokes the selective Ag+ release in their cytoplasm, and the microbot self-propulsion increases the diffusion of the released Ag+ ions. In addition, the AgNP-coated Au cap of the microbots has a dual capability of capturing bacteria and then killing them. Thus, we have demonstrated that AgNP-coated Janus microbots are capable of efficiently killing more than 80% of E. coli compared with colloidal AgNPs that killed only less than 35% of E. coli in contaminated water solutions in 15 min. After capture and extermination of bacteria, magnetic properties of the cap allow collection of microbots from water along with the captured dead bacteria, leaving water with no biological contaminants. The presented biocompatible Janus microbots offer an encouraging method for rapid disinfection of water.

JTD Keywords: Bactericidal, Magnetic control, Micromotors, Microswimmers, Self-propulsion, Silver nanoparticles


Ma, X., Sánchez, S., (2017). Bio-catalytic mesoporous Janus nano-motors powered by catalase enzyme Tetrahedron , 73, (33), 4883-4886

Enzyme triggered bio-catalytic reactions convert chemical energy into mechanical force to power micro/nano-machines. Though there have been reports about enzymes powered micro/nano-motors, enzymatic Janus nano-motor smaller than 100 nm has not been reported yet. Here, we prepared an enzyme powered Janus nano-motor by half-capping a thin layer of silicon dioxide (4 nm SiO2) onto a mesoporous silica nanoparticle (MSNP) of 90 nm, enabling asymmetry to the nano-architecture. The nano-motors are chemically powered by the decomposition of H2O2 triggered by the enzyme catalase located at one face of the nanoparticles. The self-propulsion is characterized by dynamic light scattering (DLS) and optical microscopy. The apparent diffusion coefficient was enhanced by 150% compared to their Brownian motion at low H2O2 concentration (i.e. below 3 wt%). Mesoporous nano-motors might serve as active drug delivery nano-systems in future biomedical applications such as intracellular drug delivery.

JTD Keywords: Enzyme catalysis, Janus particles, Mesoporous silica, Nano-motors, Nanomachine, Self-propulsion


Maggi, Claudio, Simmchen, Juliane, Saglimbeni, Filippo, Katuri, Jaideep, Dipalo, Michele, De Angelis, Francesco, Sánchez, Samuel, Di Leonardo, Roberto, (2016). Self-assembly of micromachining systems powered by Janus micromotors Small 12, (4), 446-451

Janus particles can self-assemble around microfabricated gears in reproducible configurations with a high degree of spatial and orientational order. The final configuration maximizes the torque applied on the rotor leading to a unidirectional and steady rotating motion. The interplay between geometry and dynamical behavior leads to the self-assembly of Janus micromotors starting from randomly distributed particles.

JTD Keywords: Active catalytic particles, Microgears, Micromachines, Janus particles, Self-assembly, Self-propulsion


Sánchez, S., Soler, L., Katuri, J., (2015). Chemically powered micro- and nanomotors Angewandte Chemie - International Edition 54, (4), 1414-1444

Chemically powered micro- and nanomotors are small devices that are self-propelled by catalytic reactions in fluids. Taking inspiration from biomotors, scientists are aiming to find the best architecture for self-propulsion, understand the mechanisms of motion, and develop accurate control over the motion. Remotely guided nanomotors can transport cargo to desired targets, drill into biomaterials, sense their environment, mix or pump fluids, and clean polluted water. This Review summarizes the major advances in the growing field of catalytic nanomotors, which started ten years ago.

JTD Keywords: Catalysis, Micromotors, Nanomotors, Robots, Self-propulsion


Seo, K. D., Kwak, B. K., Sánchez, S., Kim, D. S., (2015). Microfluidic-assisted fabrication of flexible and location traceable organo-motor IEEE Transactions on Nanobioscience , 14, (3), 298-304

In this paper, we fabricate a flexible and location traceable micromotor, called organo-motor, assisted by microfluidic devices and with high throughput. The organo-motors are composed of organic hydrogel material, poly (ethylene glycol) diacrylate (PEGDA), which can provide the flexibility of their structure. For spatial and temporal traceability of the organo-motors under magnetic resonance imaging (MRI), superparamagnetic iron oxide nanoparticles (SPION; Fe3O4) were incorporated into the PEGDA microhydrogels. Furthermore, a thin layer of platinum (Pt) was deposited onto one side of the SPION-PEGDA microhydrogels providing geometrical asymmetry and catalytic propulsion in aqueous fluids containing hydrogen peroxide solution, H2O2. Furthermore, the motion of the organo-motor was controlled by a small external magnet enabled by the presence of SPION in the motor architecture.

JTD Keywords: Flexible, Hydrogel, Magnetic resonance imaging, Microfluidics, Micromotor, Microparticle, Organo-motor, Poly (ethylene glycol) diacrylate, Self-propulsion, Superparamagnetic iron oxide nanoparticles


Khalil, I. S. M., Magdanz, V., Sánchez, S., Schmidt, O. G., Misra, S., (2015). Precise localization and control of catalytic janus micromotors using weak magnetic fields International Journal of Advanced Robotic Systems , 12, (2), 1-7

We experimentally demonstrate the precise localization of spherical Pt-Silica Janus micromotors (diameter 5 μm) under the influence of controlled magnetic fields. First, we control the motion of the Janus micromotors in two-dimensional (2D) space. The control system achieves precise localization within an average region-of-convergence of 7 μm. Second, we show that these micromotors provide sufficient propulsion force, allowing them to overcome drag and gravitational forces and move both downwards and upwards. This propulsion is studied by moving the micromotors in three-dimensional (3D) space. The micromotors move downwards and upwards at average speeds of 19.1 μm/s and 9.8 μm/s, respectively. Moreover, our closed-loop control system achieves localization in 3D space within an average region-of-convergence of 6.3 μm in diameter. The precise motion control and localization of the Janus micromotors in 2D and 3D spaces provides broad possibilities for nanotechnology applications.

JTD Keywords: 3D space, Localization, Magnetic control, Micromotors, Self-propulsion