Staff member

In recent years, enzyme-powered nanomotors (NMs) have emerged as promising tools for biomedical applications. They exhibit active motion in complex media, whereas traditional passive nanoparticles (NPs) typically remain trapped. Despite their potential, nanogels (NGs)-3D, cross-linked polymeric networks with high water retention and environmental responsiveness-remain underexplored as cores for enzymatic NMs. Here, fine-tuned NGs designed to confer smart properties are presented, allowing them to adapt their size and density in response to external stimuli (e.g., pH, temperature, and redox conditions). After anchoring urease to these NGs to produce nanogel-nanomotors (NGs-NMs), they exhibited both individual and collective motion at a very low urea concentration, enabling displacement in highly viscous environments. To achieve this, four NGs formulations based on p-(N-isopropylacrylamide) co-polymerized with p-Itaconic acid (p-(NIPAM-co-IAc)) are developed, cross-linked with either N,N '-methylenebisacrylamide (BIS) and/or N,N '-bis(acryloyl)cystamine (BAC), and coated with p-(2-hydroxyethyl methacrylate) (p-HEMA). This results, obtained via confocal microscopy and flow cytometry, demonstrate their rapid cell internalization. Moreover, synchrotron-based infrared spectroscopy (SR-FTIRM) allowed to demonstrate that NGs-NMs can tune the physicochemical composition of tumoral cells. This findings underscore the potential of NGs-NMs, combining adaptability, safety, and efficacy. They represent the evolution in NMs technology, paving the way for groundbreaking advancements in personalized medicine.

JTD Keywords: Active mater, Enzymatic nanomotors, Hydrogels, Nanobots, Nanogels, Poly(2-hydroxyethyl methacrylate), Ure, Urea, Viscous medi, Viscous media

The field of nanophotonics has seen remarkable advances, with gold-based materials standing out. By precisely fine-tuning the size and shape of metal nanoparticles (NPs), such as gold nanoparticles (AuNPs), it has been possible to gain control over light interaction, modulating localized surface plasmon resonance (LSPR), a phenomenon that involves the collective oscillation of free conduction electrons. This has opened the path toward more powerful biomedical applications, including surface-enhanced Raman spectroscopy (SERS) and photothermal therapy (PTT). When AuNPs dimensions fall below 2 nm, they become gold nanoclusters (AuNCs), losing the LSPR but acquitting fluorescence due to their molecule-like behavior. This unique feature makes them ideal for high-resolution imaging, biomarker detection, and advanced therapies. Beyond traditional uses, the recent inclusion of AuNPs into nanomotors (NMs) enhances precise in vivo tracking and targeted drug delivery. This review highlights the different applications of plasmonic nanomaterials with particular emphasis on AuNPs and AuNCs as a function of their shapes, sizes, and stabilization ligands. Moreover, it dives into the biosensing applications of plasmonic materials by addressing their so-called far-field and near-field optical properties, giving a detailed overview of different high-sensitivity immunoassays and biosensing. A comprehensive outlook on the evolution of plasmonic-based materials for the next therapies is provided.

JTD Keywords: Albumin-gold nanoclusters, Cancer-cells, Gold nanoparticles, Intracellular ph, Microwave-assisted synthesis, Nanoclusters, Nanomotors, Optical-properties, Plasmonic biosensors, Protein-directed synthesis, Rapid synthesi, Resonance immunoassay, Ser, Sers, Silver nanoparticles, Ultrasensitive detection

Living organisms, from single cells to multicellular systems, are capable of moving as a response to local stimuli using swarming intelligence, a trait researchers aim to replicate in artificial systems. Common strategies observed in natural swarms include motility towards specific signals from the environment, communication among individual units, coordination and cooperation to achieve complex tasks. Inspired by these features, the focus in bioinspired motile nanosystems has shifted from studying individual units to exploring and controlling collective behaviours. Various propulsion mechanisms including magnetic, electric or acoustic fields, as well as onboard chemical reactions, have enabled artificial micromotor and nanomotor (MNM) swarms that can move collectively as a response to environmental inputs. The controlled navigation and improved tissue penetration of MNM swarms is promising within the biomedical field, including in the active transport of medical agents. Despite these exciting advances, artificial MNMs still fall short of the complexity and autonomy seen in biological systems. This Perspective explores the collective behaviour of biological swarms and bioinspired artificial self-propelled nanosystems. We discuss how swarming intelligence applied to synthetic active nanosystems enables swarms to perform various tasks. Finally, we discuss challenges, including material limitations, information storage, communication between swarms and prospects for intelligent swarming systems.

JTD Keywords: Acoustic propulsion, Behavior, Chemical communication, Chemotaxis, Drive, Mechanisms, Nanorod motors, Ph taxis, Powered nanomotors, Supramolecular nanomotors

The contractile nature of skeletal muscle tissue makes it especially attractive for powering biohybrid actuators. Significant efforts have been dedicated to the improvement and control of contraction force, going one step forward toward the automation of these biohybrid platforms. Herein, 3D-bioengineered skeletal muscle tissues are integrated with organic transistor-based sensors to define a soft bioactuator with real-time force monitoring capabilities. The muscle tissue is electrically stimulated while the organic sensor ensures transduction of the exerted force into an electrical signal that allows direct monitoring of the bioactuator performance. Sensor calibration is carried out to define its sensitivity at different biasing conditions: as opposed to standard, two-terminal piezoresistive devices, transistor-based strain sensors show tunable sensitivity by acting on the voltage applied to a third terminal-the gate. A complete evaluation of sensing performances is provided, demonstrating that real-time monitoring is effective under different conditions, including stimulation signal frequency and chemical modulation of the bioactuator contraction, demonstrating its potential use as a drug testing platform. In the reported results, the way is paved for a complete exploitation of organic devices in soft robotic applications and to the development of novel biohybrid machines in bioengineering and biomedicine. The integration of sensing elements in bioengineered actuators is key to obtain real-time information about their performance and further control/automation. By coupling flexible organic field-effect transistor to a skeletal muscle actuator we demonstrate the feasibility to record in real-time its contractile behavior when stimulated by electrical pulses, showing both high sensitivity absence of cross talk between stimulation and readout.image (c) 2024 WILEY-VCH GmbH

JTD Keywords: Bioengineerings, Flexible electronics, Muscle-based actuators, Organic field-effect transistors, Soft robotic

Skeletal muscle tissue represents an attractive powering component for biohybrid robots, as traditional actuators used in the soft robotic context often rely on complex mechanisms and lack scalability at small dimensions. This article proposes a monolithic biohybrid flexure mechanism actuated by a bioengineered skeletal muscle tissue. The design leverages the contractile properties of a bioengineered skeletal muscle to produce a bending motion in a monolithic, tubular mechanism made of a soft and biocompatible silicone blend. This structure integrates two cylindrical pillars that facilitate force transmission from the bioengineered muscle tissue. Performance assessments reveal excellent contractile and stable behavior upon electrical stimulation, compared to current biohybrid actuation systems, with enhanced performance as the mechanism's internal and external diameters decrease. Finite-element simulations further reveal distinct force-displacement responses in mechanisms with different flexural rigidity. This innovative, scalable, and easy-to-fabricate design represents a significant step forward in the development of novel biohybrid machines.

JTD Keywords: Bioactuator, Biohybrid robotics, Flexible skeleton, Microfabrication, Muscle contraction, Muscle tissue engineering, Soft robotic

Advances in 3D bioprinting have opened new possibilities for developing bioengineered muscle models that can mimic the architecture and function of native tissues. However, current bioengineering approaches do not fully recreate the complex fascicle-like hierarchical organization of the skeletal muscle tissue, impacting on the muscle maturation due to the lack of oxygen and nutrient supply in the scaffold inner regions. A key challenge is the production of precise and width-controlled independent filaments that do not fuse during the printing process when subsequently extruded, ensuring the formation of fascicle-like structures. This study addresses the limitation of filament fusion by utilizing a pluronic-assisted co-axial 3D bioprinting system (PACA-3D) creates a physical confinement of the bioink during the extrusion process, effectively obtaining thin and independent printed filaments with controlled shapes. The use of PACA-3D enabled the fabrication of skeletal muscle-based bioactuators with improved cell differentiation and significantly increased force output, obtaining 3 times stronger bioengineered muscle when compared to bioactuators fabricated using conventional 3D extrusion bioprinting techniques, where a single syringe containing the bioink is used. The versatility of our technology has been demonstrated using different biomaterials, demonstrating its potential to develop more complex biohybrid tissue-based architectures with improved functionality, as well as aiming for better scalability and printing flexibility.

JTD Keywords: 3d bioprinting, Bioengineering, Cells, Co-axial printin, Collagen, Constructs, Gelati, Muscle-based actuators, Pluronic, Tissue

Most non-muscle invasive bladder cancers have been treated by transurethral resection and following intravesical injection of immunotherapeutic agents. However, the delivery efficiency of therapeutic agents into bladder wall is low due to frequent urination, which leads to the failure of treatment with side effects. Here, we report a urease-powered nanomotor containing the agonist of stimulator of interferon genes (STING) for the efficient activation of immune cells in the bladder wall. After characterization, we perform in vitro motion analysis and assess in vivo swarming behaviors of nanomotors. The intravesical instillation results in the effective penetration and retention of nanomotors in the bladder. In addition, we confirm the anti-tumor effect of nanomotor containing the STING agonist (94.2% of inhibition), with recruitment of CD8+ T cells (11.2-fold compared with PBS) and enhanced anti-tumor immune responses in bladder cancer model in female mice. Furthermore, we demonstrate the better anti-tumor effect of nanomotor containing the STING agonist than those of the gold standard Bacille Calmette-Guerin therapy and the anti-PD-1 inhibitor pembrolizumab in bladder cancer model. Taken together, the urease-powered nanomotor would provide a paradigm as a next-generation platform for bladder cancer immunotherapy. Self-propelling micro/nanomotors represent a therapeutic option for drug delivery. Here the authors report the design and characterization of a biodegradable urease-powered nanomotor containing STING agonist, promoting anti-tumor immune responses in bladder cancer models.

JTD Keywords: Cellular uptake, Pathwa, Pembrolizumab

An introduction to the Nanoscale and Journal of Materials Chemistry B themed collection on micro- and nano-motors that features a series of articles discussing the virtue of their small size and controllable mobility, while highlighting the revolutionary potential applications.

JTD

We report the fabrication and characterization of a highly sensitive pressure sensor that has been successfully tested using 3D-bioprinted skeletal muscle tissue. The proposed pressure sensor consists of two assembled 3D printed specimens, which were obtained using 60/40 v/v poly(3,4-ethylenedioxythiophene):polystyrene sulfonic acid (PEDOT:PSS) / poly(ethylene glycol) diacrylate (PEGDA) mixture, placed between two indium tin oxidecoated polyethylene terephthalate (PET-ITO) films. The printed specimens were shaped with a serrated structure, improving the sensitivity of the contact when pressed against PET-ITO film. Initially, the performance of the fabricated pressure sensor was tested using light cylindrical weights, which corresponded to pressures ranging from 0.99 to 14.71 kPa, and as prove of concept, carefully pressing with the finger (from 2.91 to 6.81 kPa). As the sensitivity and fast response of sensor were compatible with detection of soft muscle contractions, 3D-bioprinted skeletal muscle bioactuators were manufactured using myoblast cells. The contractions of the bioactuators, which were induced using electrical stimulation, exerted a pressure of 1.5 kPa only that was clearly and precisely detected by the sensor. Overall, the potential application of proposed pressure sensor for wearable and biomedical devices is evidenced by demonstrating its fast response time (< 50 ms) and sensitivity.

JTD Keywords: 4-ethylenedioxythiophene), Bioactuator, Healt, Hydrogels, Poly(3, Poly(ethylene glycol) diacrylate, Raman-spectroscopy, Soft electronics, Wearable electronic

This study investigates the synthesis and optimization of nanobots (NBs) loaded with pDNA using the layer-by-layer (LBL) method and explores the impact of their collective motion on the transfection efficiency. NBs consist of biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and are powered by the urease enzyme, enabling autonomous movement and collective swarming behavior. In vitro experiments were conducted to validate the delivery efficiency of fluorescently labeled NBs, using two-dimensional (2D) and three-dimensional (3D) cell models: murine urothelial carcinoma cell line (MB49) and spheroids from human urothelial bladder cancer cells (RT4). Swarms of pDNA-loaded NBs showed enhancements of 2.2- to 2.6-fold in delivery efficiency and 6.8- to 8.1-fold in material delivered compared to inhibited particles (inhibited enzyme) and the absence of fuel in a 2D cell culture. Additionally, efficient intracellular delivery of pDNA was demonstrated in both cell models by quantifying and visualizing the expression of eGFP. Swarms of NBs exhibited a >5-fold enhancement in transfection efficiency compared to the absence of fuel in a 2D culture, even surpassing the Lipofectamine 3000 commercial transfection agent (cationic lipid-mediated transfection). Swarms also demonstrated up to a 3.2-fold enhancement in the amount of material delivered in 3D spheroids compared to the absence of fuel. The successful transfection of 2D and 3D cell cultures using swarms of LBL PLGA NBs holds great potential for nucleic acid delivery in the context of bladder treatments.

JTD Keywords: Animals, Barrier, Cell line, tumor, Dna, Drug delivery, Drug-delivery, Enzyme catalysis, Gene delivery, Gene transfer techniques, Humans, Lactic acid, Mice, Nanobots, Nanoparticles, Pdna, Plasmids, Polyglycolic acid, Polylactic acid-polyglycolic acid copolymer, Swarming, Transfectio, Transfection, Urease, Urinary bladder neoplasms

Biological barriers present a significant obstacle to treatment, especially when drugs are administered locally to increase their concentrations at the target site while minimizing unintended off-target effects. Among these barriers, mucus presents a challenge, as it serves as a protective layer in the respiratory, urogenital, and gastrointestinal tracts. Its role is to shield the underlying epithelial cells from pathogens and toxic compounds but also impedes the efficient delivery of drugs. Despite the exploration of mucolytic agents to improve drug delivery, overcoming this protective barrier remains a significant hurdle. In our study, we investigate an alternative approach involving the use of catalase-powered nanobots. We use an in vitro model that simulates intestinal mucus secretion to demonstrate the dual functionality of our nanobots. This includes their ability to disrupt mucus, which we confirmed through in vitro and ex vivo validation, as well as their self-propulsion to overcome the mucus barrier, resulting in a 60-fold increase compared with passive nanoparticles. Therefore, our findings highlight the potential utility of catalase-powered nanobots as carriers for therapeutic agents since they could enhance drug delivery efficiency by penetrating the mucus barrier.

JTD Keywords: Biological barrier, Biological barriers, Drug-delivery, Growth, Hydrogen-peroxide, Muci, Mucus, Nanobots, Nanomedicine, Nanomotors, Transport

Here, we report DNA-based synthetic nanostructures decorated with enzymes (hereafter referred to as DNA-enzyme swimmers) that self-propel by converting the enzymatic substrate to the product in solution. The DNA-enzyme swimmers are obtained from tubular DNA structures that self-assemble spontaneously by the hybridization of DNA tiles. We functionalize these DNA structures with two different enzymes, urease and catalase, and show that they exhibit concentration-dependent movement and enhanced diffusion upon addition of the enzymatic substrate (i.e., urea and H2O2). To demonstrate the programmability of such DNA-based swimmers, we also engineer DNA strands that displace the enzyme from the DNA scaffold, thus acting as molecular brakes on the DNA swimmers. These results serve as a first proof of principle for the development of synthetic DNA-based enzyme-powered swimmers that can self-propel in fluids.

JTD Keywords: Biocatalysis, Catalase, Design, Dna, Hydrogen peroxide, Motor, Nanostructures, Shapes, Urease

Over the past decades, the development of nanoparticles (NPs) to increase the efficiency of clinical treatments has been subject of intense research. Yet, most NPs have been reported to possess low efficacy as their actuation is hindered by biological barriers. For instance, synovial fluid (SF) present in the joints is mainly composed of hyaluronic acid (HA). These viscous media pose a challenge for many applications in nanomedicine, as passive NPs tend to become trapped in complex networks, which reduces their ability to reach the target location. This problem can be addressed by using active NPs (nanomotors, NMs) that are self-propelled by enzymatic reactions, although the development of enzyme-powered NMs, capable of navigating these viscous environments, remains a considerable challenge. Here, the synergistic effects of two NMs troops, namely hyaluronidase NMs (HyaNMs, Troop 1) and urease NMs (UrNMs, Troop 2) are demonstrated. Troop 1 interacts with the SF by reducing its viscosity, thus allowing Troop 2 to swim more easily through the SF. Through their collective motion, Troop 2 increases the diffusion of macromolecules. These results pave the way for more widespread use of enzyme-powered NMs, e.g., for treating joint injuries and improving therapeutic effectiveness compared with traditional methods. The conceptual idea of the novel approach using hyaluronidase NMs (HyaNMs) to interact with and reduce the viscosity of the synovial fluid (SF) and urease NMs (UrNMs) for a more efficient transport of therapeutic agents in joints.image

JTD Keywords: Biological barrier, Clinical research, Clinical treatments, Collective motion, Collective motion,nanomotors,nanorobots,swarming,viscous medi, Collective motions, Complex networks, Enzymatic reaction, Enzymes, Hyaluronic acid, Hyaluronic-acid,ph,viscoelasticity,adsorption,barriers,behavior,ureas, Macromolecules, Medical nanotechnology, Nano robots, Nanomotors, Nanorobots, Swarming, Synovial fluid, Target location, Viscous media, Viscous medium

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

The interaction of nanoparticles with biological media is a topic of general interest for drug delivery systems and among those for active nanoparticles, also called nanomotors. Herein, we report the use of super resolution microscopy, in particular, stochastic optical reconstruction microscopy (STORM), to characterize the formation of a protein corona around active enzyme-powered nanomotors. First, we characterized the distribution and number of enzymes on nano-sized particles and characterized their motion capabilities. Then, we incubated the nanomotors with fluorescently labelled serum proteins. Interestingly, we observed a significant decrease of protein corona formation (20%) and different composition, which was studied by proteomic analysis. Moreover, motion was not hindered, as nanomotors displayed enhanced diffusion regardless of the protein corona. Elucidating how active particles interact with biological media and maintain their self-propulsion after protein corona formation will pave the way for the use of these systems in complex biological fluids in biomedicine.; The interaction of self-propelled nanomotors with biological media is of outmost relevance when considering their actuation within biological contexts. Here, we explored how protein corona forms around active nanomotors using STORM.

JTD Keywords: Gold, Impact, Nanoparticle uptake, Plasma, Size, Surface-properties

Targeted drug delivery depends on the ability of nanocarriers to reach the target site, which requires the penetration of different biological barriers. Penetration is usually low and slow because of passive diffusion and steric hindrance. Nanomotors (NMs) have been suggested as the next generation of nanocarriers in drug delivery due to their autonomous motion and associated mixing hydrodynamics, especially when acting collectively as a swarm. Here, we explore the concept of enzyme-powered NMs designed as such that they can exert disruptive mechanical forces upon laser irradiation. The urease-powered motion and swarm behavior improve translational movement compared to passive diffusion of state-of-the-art nanocarriers, while optically triggered vapor nanobubbles can destroy biological barriers and reduce steric hindrance. We show that these motors, named Swarm 1, collectively displace through a microchannel blocked with type 1 collagen protein fibers (barrier model), accumulate onto the fibers, and disrupt them completely upon laser irradiation. We evaluate the disruption of the microenvironment induced by these NMs (Swarm 1) by quantifying the efficiency by which a second type of fluorescent NMs (Swarm 2) can move through the cleared microchannel and be taken up by HeLa cells at the other side of the channel. Experiments showed that the delivery efficiency of Swarm 2 NMs in a clean path was increased 12-fold in the presence of urea as fuel compared to when no fuel was added. When the path was blocked with the collagen fibers, delivery efficiency dropped considerably and only depicted a 10-fold enhancement after pretreatment of the collagen-filled channel with Swarm 1 NMs and laser irradiation. The synergistic effect of active motion (chemically propelled) and mechanical disruption (light-triggered nanobubbles) of a biological barrier represents a clear advantage for the improvement of therapies which currently fail due to inadequate passage of drug delivery carriers through biological barriers.

JTD Keywords: drug delivery, enzyme catalysis, nanoparticles, swarming, vapor nanobubbles, Drug carriers, Drug delivery, Drug delivery systems, Enzyme catalysis, Hela cells, Humans, Nanomotors, Nanoparticles, Swarming, Vapor nanobubbles

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

Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active b1-integrin content on the surface of Cav1KO fibroblasts. FRAP analysis and endocytosis/recycling assays revealed that active b1-integrin is mostly endocytosed through the CLIC/GEEC pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4 and PM tension-dependent manner. Moreover, the threshold for PM tension-driven b1-integrin activation is lower in Cav1KO MEFs than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response.© 2022, Lolo et al.

JTD Keywords: adhesion, alpha-v-beta-3, cell, integrin activation, internalization, kinase, mechanosensing, mediated endocytosis, mouse, stiffness, talin, trafficking, Animals, Caveolae, Cell adhesion, Cell biology, Fibroblasts, Integrin activation, Integrin beta1, Integrin recycling, Integrins, Mechanosensing, Membrane tension, Mice, Mouse, Stress, mechanical

Nanoparticles represent a promising class of material for nanomedicine and molecular biosensing. The formation of a protein corona due to nonspecific particle-protein interactions is a determining factor for the biological fate of nanoparticles in vivo and strongly impacts the performance of nanoparticles when used as biosensors. Nonspecific interactions are usually highly heterogeneous, yet little is known about the heterogeneity of the protein corona that may lead to inter- and intraparticle differences in composition and protein distribution. Here, we present a super-resolution microscopic approach to study the protein corona on single silica nanoparticles and subsequent cellular interactions using multicolor stimulated emission depletion (STED) microscopy. We demonstrate that STED resolves structural features of protein corona on single particles including the distribution on the particle surface and the degree of protein internalization in porous particles. Using multicolor measurements of multiple labeled protein species, we determine the composition of the protein corona at the single-particle level. We quantify particle-to-particle differences in the composition and find that the composition is considerably influenced by the particle geometry. In a subsequent cellular uptake measurement, we demonstrate multicolor STED of protein corona on single particles internalized by cells. Our study shows that STED microscopy opens the window toward mechanistic understanding of protein coronas and aids in the rational design of nanoparticles as nanomedicines and biosensors.

JTD Keywords: insights, multicolor microscopy, nanoparticles, protein corona, quantification, size, sted microscopy, Fluorescence, Quantification, Sted microscopy

The presence of organic pollutants in the environment is a global threat to human health and ecosystems due to their bioaccumulation and long-term persistence. Hereby a micromotor-in-sponge concept is presented that aims not only at pollutant removal, but towards an efficient in situ degradation by exploiting the synergy between the sponge hydrophobic nature and the rapid pollutant degradation promoted by the cobalt-ferrite (CFO) micromotors embedded at the sponge's core. Such a platform allows the use of extremely low fuel concentration (0.13% H2 O2 ), as well as its reusability and easy recovery. Moreover, the authors demonstrate an efficient multicycle pollutant degradation and treatment of large volumes (1 L in 15 min) by using multiple sponges. Such a fast degradation process is due to the CFO bubble-propulsion motion mechanism, which induces both an enhanced fluid mixing within the sponge and an outward flow that allows a rapid fluid exchange. Also, the magnetic control of the system is demonstrated, guiding the sponge position during the degradation process. The micromotor-in-sponge configuration can be extrapolated to other catalytic micromotors, establishing an alternative platform for an easier implementation and recovery of micromotors in real environmental applications.© 2022 Wiley-VCH GmbH.

JTD Keywords: effective removal, fabrication, microbots, microjets, organic pollutants, propelled micromotors, self-propelled micromotors, sponges, water treatment, Oil-water separation, Organic pollutants, Water treatment

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

Three-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modeling, the bioengineered muscle is treated with tumor necrosis factor α to mimic the conditions of aging, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline® Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.

JTD Keywords: 3d bioprinting, bio-actuator, drug testing, human skeletal muscle, muscle ageing, platform, tnf-alpha, 3d bioprinting, Aged, Aging, Bio-actuator, Bioprinting, Drug testing, Human skeletal muscle, Humans, Muscle ageing, Muscle, skeletal, Necrosis-factor-alpha, Pharmaceutical preparations, Tissue engineering

© 2021 Wiley Periodicals LLC. Biohybrid robotics is a field in which biological entities are combined with artificial materials in order to obtain improved performance or features that are difficult to mimic with hand-made materials. Three main level of integration can be envisioned depending on the complexity of the biological entity, ranging from the nanoscale to the macroscale. At the nanoscale, enzymes that catalyze biocompatible reactions can be used as power sources for self-propelled nanoparticles of different geometries and compositions, obtaining rather interesting active matter systems that acquire importance in the biomedical field as drug delivery systems. At the microscale, single enzymes are substituted by complete cells, such as bacteria or spermatozoa, whose self-propelling capabilities can be used to transport cargo and can also be used as drug delivery systems, for in vitro fertilization practices or for biofilm removal. Finally, at the macroscale, the combinations of millions of cells forming tissues can be used to power biorobotic devices or bioactuators by using muscle cells. Both cardiac and skeletal muscle tissue have been part of remarkable examples of untethered biorobots that can crawl or swim due to the contractions of the tissue and current developments aim at the integration of several types of tissue to obtain more realistic biomimetic devices, which could lead to the next generation of hybrid robotics. Tethered bioactuators, however, result in excellent candidates for tissue models for drug screening purposes or the study of muscle myopathies due to their three-dimensional architecture. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

JTD Keywords: bacteria-bots, based biorobots, biorobots, bots, enzymatic nanomotors, hybrid robotics, muscle‐, Bacteria‐, Bacteria-bots, Biomimetic materials, Biorobots, Enzymatic nanomotors, Humans, Hybrid robotics, Muscle-based biorobots, Nanoparticles, Nanotechnology, Robotics

Collective guidance of out-of-equilibrium systems without using external fields is a challenge of paramount importance in active matter, ranging from bacterial colonies to swarms of self-propelled particles. Designing strategies to guide active matter and exploiting enhanced diffusion associated to its motion will provide insights for application from sensing, drug delivery to water remediation. However, achieving directed motion without breaking detailed balance, for example by asymmetric topographical patterning, is challenging. Here we engineer a two-dimensional periodic topographical design with detailed balance in its unit cell where we observe spontaneous particle edge guidance and corner accumulation of self-propelled particles. This emergent behaviour is guaranteed by a second-order non-Hermitian skin effect, a topologically robust non-equilibrium phenomenon, that we use to dynamically break detailed balance. Our stochastic circuit model predicts, without fitting parameters, how guidance and accumulation can be controlled and enhanced by design: a device guides particles more efficiently if the topological invariant characterizing it is non-zero. Our work establishes a fruitful bridge between active and topological matter, and our design principles offer a blueprint to design devices that display spontaneous, robust and predictable guided motion and accumulation, guaranteed by out-of-equilibrium topology.

JTD

Catalytically powered micro/nanobots (MNBs) can perform active movement by harnessing energy from in situ chemical reactions and show tremendous potential in biomedical applications. However, the development of imageable MNBs that are driven by bioavailable fuels and possess multiple therapeutic functions remains challenging. To resolve such issues, we herein propose enzyme (urease) powered liquid metal (LM) nanobots that are naturally of multiple therapeutic functions and imaging signals. The main body of the nanobot is composed of a biocompatible LM nanoparticle encapsulated by polydopamine (PDA). Urease enzyme needed for the powering and desired drug molecules, e.g., cefixime trihydrate antibiotic, are grafted on external surfaces of the PDA shell. Such a chemical composition endows the nanobots with dual-mode ultrasonic (US) and photoacoustic (PA) imaging signals and favorable photothermal effect. These LM nanobots exhibit positive chemotaxis and therefore can be collectively guided along a concentration gradient of urea for targeted transportation. When exposed to NIR light, the LM nanobots would deform and complete the function change from active drug carriers to photothermal reagents, to achieve synergetic antibacterial treatment by both photothermal and chemotherapeutic effects. The US and PA properties of the LM nanoparticle can be used to not only track and monitor the active movement of the nanobots in a microfluidic vessel model but also visualize their dynamics in the bladder of a living mouse in vivo. To conclude, the LM nanobots demonstrated herein represent a proof-of-concept therapeutic nanosystem with multiple biomedical functionalities, providing a feasible tool for preclinical studies and clinical trials of MNB-based imaging-guided therapy.

JTD Keywords: cell, chemo-photothermal therapy, chemotaxis, image tracking, liquid metal nanobots, nanomotors, tracking, Chemo-photothermal therapy, Chemotaxis, Image tracking, Liquid metal nanobots, Nanomotors

Bioinspired hybrid soft robots that combine living and synthetic components are an emerging field in the development of advanced actuators and other robotic platforms (i.e., swimmers, crawlers, and walkers). The integration of biological components offers unique characteristics that artificial materials cannot precisely replicate, such as adaptability and response to external stimuli. Here, we present a skeletal muscle–based swimming biobot with a three-dimensional (3D)–printed serpentine spring skeleton that provides mechanical integrity and self-stimulation during the cell maturation process. The restoring force inherent to the spring system allows a dynamic skeleton compliance upon spontaneous muscle contraction, leading to a cyclic mechanical stimulation process that improves the muscle force output without external stimuli. Optimization of the 3D-printed skeletons is carried out by studying the geometrical stiffnesses of different designs via finite element analysis. Upon electrical actuation of the muscle tissue, two types of motion mechanisms are experimentally observed: directional swimming when the biobot is at the liquid-air interface and coasting motion when it is near the bottom surface. The integrated compliant skeleton provides both the mechanical self-stimulation and the required asymmetry for directional motion, displaying its maximum velocity at 5 hertz (800 micrometers per second, 3 body lengths per second). This skeletal muscle–based biohybrid swimmer attains speeds comparable with those of cardiac-based biohybrid robots and outperforms other muscle-based swimmers. The integration of serpentine-like structures in hybrid robotic systems allows self-stimulation processes that could lead to higher force outputs in current and future biomimetic robotic platforms. Copyright © 2021 The Authors, some rights reserved;

JTD Keywords: actuators, design, fabrication, mechanics, mems, myotubes, platform, tissue, 3d printers, Agricultural robots, Animals, Artificial organs, Biological components, Biomimetic materials, Biomimetic processes, Biomimetics, Cell line, Electrical actuation, Equipment design, Finite element analysis, Geometrical stiffness, Intelligent robots, Liquefied gases, Liquid-air interface, Mechanical integrity, Mechanical phenomena, Mechanical stimulation, Mice, Motion, Muscle, Muscle contractions, Muscle, skeletal, Phase interfaces, Printing, three-dimensional, Robotics, Serpentine, Smart materials, Springs (components), Swimming, Threedimensional (3-d), Tissue scaffolds

Chemically active Janus particles sustain non-equilibrium spatial variations in the chemical composition of the suspending solution; these induce hydrodynamic flow and (self-)motility of the particles. Direct mapping of these fields has so far proven to be too challenging. Therefore, indirect methods are needed, e.g., deconvolving the response of “tracer” particles to the activity-induced fields. Here, we study experimentally the response of silica particles, sedimented at a wall, to active Pt/silica Janus particles. The latter are either immobilized at the wall, with the symmetry axis perpendicular or parallel to the wall, or motile. The experiments reveal complex effective interactions that are dependent on the configuration and on the state of motion of the active particle. Within the framework of a coarse-grained model, the behavior of tracers near an immobilized Janus particle can be captured qualitatively once activity-induced osmotic flows on the wall are considered.

JTD Keywords: sphere, Motion

Enzyme-powered nanomotors are an exciting technology for biomedical applications due to their ability to navigate within biological environments using endogenous fuels. However, limited studies into their collective behavior and demonstrations of tracking enzyme nanomotors in vivo have hindered progress toward their clinical translation. Here, we report the swarming behavior of urease-powered nanomotors and its tracking using positron emission tomography (PET), both in vitro and in vivo. For that, mesoporous silica nanoparticles containing urease enzymes and gold nanoparticles were used as nanomotors. To image them, nanomotors were radiolabeled with either I on gold nanoparticles or F-labeled prosthetic group to urease. In vitro experiments showed enhanced fluid mixing and collective migration of nanomotors, demonstrating higher capability to swim across complex paths inside microfabricated phantoms, compared with inactive nanomotors. In vivo intravenous administration in mice confirmed their biocompatibility at the administered dose and the suitability of PET to quantitatively track nanomotors in vivo. Furthermore, nanomotors were administered directly into the bladder of mice by intravesical injection. When injected with the fuel, urea, a homogeneous distribution was observed even after the entrance of fresh urine. By contrast, control experiments using nonmotile nanomotors (i.e., without fuel or without urease) resulted in sustained phase separation, indicating that the nanomotors’ self-propulsion promotes convection and mixing in living reservoirs. Active collective dynamics, together with the medical imaging tracking, constitute a key milestone and a step forward in the field of biomedical nanorobotics, paving the way toward their use in theranostic applications. 124 18

JTD Keywords: cell, reversal, silica nanoparticles, size, step, transport, Administration, intravesical, Animals, Equipment design, Female, Gold, Metal nanoparticles, Mice, Mice, inbred c57bl, Motion, Phantoms, imaging, Positron emission tomography computed tomography, Precision medicine, Propelled micromotors, Robotics, Translational research, biomedical, Urease, Urinary bladder

© 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

Here, we report the design, synthesis, and functional testing of enzyme-powered porous micromotors built from a metal–organic framework (MOF). We began by subjecting a presynthesized microporous UiO-type MOF to ozonolysis, to confer it with mesopores sufficiently large to adsorb and host the enzyme catalase (size: 6–10 nm). We then encapsulated catalase inside the mesopores, observing that they are hosted in those mesopores located at the subsurface of the MOF crystals. In the presence of H2O2 fuel, MOF motors (or MOFtors) exhibit jet-like propulsion enabled by enzymatic generation of oxygen bubbles. Moreover, thanks to their hierarchical pore system, the MOFtors retain sufficient free space for adsorption of additional targeted species, which we validated by testing a MOFtor for removal of rhodamine B during self-propulsion.

JTD

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

We examine a mechanism of locomotion of active particles whose surface is uniformly coated with mobile enzymes. The enzymes catalyze a reaction that drives phoretic flows but their homogeneous distribution forbids locomotion by symmetry. We find that the ability of the enzymes to migrate over the surface combined with self-phoresis can lead to a spontaneous symmetry-breaking instability whereby the homogeneous distribution of enzymes polarizes and the particle propels. The instability is driven by the advection of enzymes by the phoretic flows and occurs above a critical Péclet number. The transition to polarized motile states occurs via a supercritical or subcritical pitchfork bifurcations, the latter of which enables hysteresis and coexistence of uniform and polarized states.

JTD Keywords: Biomimetic & bio-inspired materials, Locomotion, Surface-driven phase separation

The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nanomotors holds enormous potential in a number of applications in the biomedical field. Herein, we report the preparation of mesoporous silica nanoparticles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules ([Ru(bpy)3]Cl2 (bpy = 2,2′-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both [Ru(bpy)3]Cl2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to “sense” the environment and deliver the payload on demand in response to predefined stimuli.

JTD Keywords: Controlled release, Drug delivery, Enzymatic catalysis, Gatekeepers, Nanocarriers, Nanomotors, Stimuli-responsive nanomaterials

Artificial microswimmers have the potential for applications in many fields, ranging from targeted cargo delivery and mobile sensing to environmental remediation. In many of these applications, the artificial swimmers will operate in complex media necessarily involving liquid–liquid interfaces. Here, we experimentally study the motion of chemically powered phoretic active colloids close to liquid–liquid interfaces while swimming next to a solid substrate. In a system involving this complex geometry, we find that the active particles have an alignment interaction with both the neighbouring solid and liquid interfaces, allowing for a robust guiding mechanism along the liquid interface. We compare with minimal active Brownian simulations to show that these phoretically active particles stay along the interfaces for much longer times and lengths than expected for standard active Brownian particles. We also track the propulsion speeds of these particles and find a reduced speed close to the liquid–liquid interface. We report an interesting non-linear dependence of this reduction on the particle's bulk speed..

JTD

The field of bio-hybrid robotics aims at the integration of biological components with artificial materials in order to take advantage of many unique features occurring in nature, such as adaptability, self-healing or resilience. In particular, skeletal muscle tissue has been used to fabricate bio-actuators or bio-robots that can perform simple actions. In this paper, we present 3D bioprinting as a versatile technique to develop these kinds of actuators and we focus on the importance of optimizing the designs and properly characterizing their performance. For that, we introduce a method to calculate the force generated by the bio-actuators based on the deflection of two posts included in the bio-actuator design by means of image processing algorithms. Finally, we present some results related to the adaptation, controllability and force modulation of our bio-actuators, paving the way towards a design- and optimization-driven development of more complex 3D-bioprinted bio-actuators.

JTD Keywords: 3D bioprinting, Bio-hybrid robotics, Muscle-based bio-actuators

The use of enzyme catalysis to power micro- and nanomotors exploiting biocompatible fuels has opened new ventures for biomedical applications such as the active transport and delivery of specific drugs to the site of interest. Here, urease-powered nanomotors (nanobots) for doxorubicin (Dox) anticancer drug loading, release, and efficient delivery to cells are presented. These mesoporous silica-based core-shell nanobots are able to self-propel in ionic media, as confirmed by optical tracking and dynamic light scattering analysis. A four-fold increase in drug release is achieved by nanobots after 6 h compared to their passive counterparts. Furthermore, the use of Dox-loaded nanobots presents an enhanced anticancer efficiency toward HeLa cells, which arises from a synergistic effect of the enhanced drug release and the ammonia produced at high concentrations of urea substrate. A higher content of Dox inside HeLa cells is detected after 1, 4, 6, and 24 h incubation with active nanobots compared to passive Dox-loaded nanoparticles. The improvement in drug delivery efficiency achieved by enzyme-powered nanobots may hold potential toward their use in future biomedical applications such as the substrate-triggered release of drugs in target locations.

JTD Keywords: Drug delivery, Enzymatic catalysis, Nanobots, Nanomachines, Nanomotors

Self-propelled micromotors have previously shown to enhance pollutant removal compared to non-motile nano-micro particles. However, these systems are expensive, difficult to scale-up and require surfactant for efficient work. Efficient and inexpensive micromotors are desirable for their practical applications in water treatment technologies. We describe cobalt-ferrite based micromotors (CFO micromotors) fabricated by a facile and scalable synthesis, that produce hydroxyl radicals via Fenton-like reaction and take advantage of oxygen gas generated during this reaction for self-propulsion. Once the reaction is complete, the CFO micromotors can be easily separated and collected due to their magnetic nature. The CFO micromotors are demonstrated for highly efficient advanced oxidative removal of tetracycline antibiotic from the water. Furthermore, the effects of different concentrations of micromotors and hydrogen peroxide on the antibiotic degradation were studied, as well as the generation of the highly reactive hydroxyl radicals responsible for the oxidation reaction.

JTD Keywords: Degradation, Fenton reaction, Microbots, Nanomotors, Self-propelled Micromotors, Water treatment

Bacteria biohybrids employ the motility and power of swimming bacteria to carry and maneuver microscale particles. They have the potential to perform microdrug and cargo delivery in vivo, but have been limited by poor design, reduced swimming capabilities, and impeded functionality. To address these challenge, motile Escherichia coli are captured inside electropolymerized microtubes, exhibiting the first report of a bacteria microswimmer that does not utilize a spherical particle chassis. Single bacterium becomes partially trapped within the tube and becomes a bioengine to push the microtube though biological media. Microtubes are modified with "smart" material properties for motion control, including a bacteria-attractant polydopamine inner layer, addition of magnetic components for external guidance, and a biochemical kill trigger to cease bacterium swimming on demand. Swimming dynamics of the bacteria biohybrid are quantified by comparing "length of protrusion" of bacteria from the microtubes with respect to changes in angular autocorrelation and swimmer mean squared displacement. The multifunctional microtubular swimmers present a new generation of biocompatible micromotors toward future microbiorobots and minimally invasive medical applications.

JTD Keywords: Biohybrids, E. coli, Micromotors, Microswimmers, Polydopamine

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

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

Self-powered micromachines are promising tools for future environmental remediation technology. Waste-water treatment and water reuse is an essential part of environmental sustainability. Herein, we present reusable Fe/Pt multi-functional active microcleaners that are capable of degrading organic pollutants (malachite green and 4-nitrophenol) by generated hydroxyl radicals via a Fenton-like reaction. Various different properties of microcleaners, such as the effect of their size, short-term storage, long-term storage, reusability, continuous swimming capability, surface composition, and mechanical properties, are studied. It is found that these microcleaners can continuously swim for more than 24 hours and can be stored more than 5 weeks during multiple cleaning cycles. The produced microcleaners can also be reused, which reduces the cost of the process. During the reuse cycles the outer iron surface of the Fe/Pt microcleaners generates the in-situ, heterogeneous Fenton catalyst and releases a low concentration of iron into the treated water, while the mechanical properties also appear to be improved due to both its surface composition and structural changes. The microcleaners are characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), nanoindentation, and finite-element modeling (FEM).

JTD Keywords: Catalysts, Heterogeneous catalysis, Microcleaners, Micromotors, Nanorobots, Wastewater treatment

Achieving control over the directionality of active colloids is essential for their use in practical applications such as cargo carriers in microfluidic devices. So far, guidance of spherical Janus colloids was mainly realized using specially engineered magnetic multilayer coatings combined with external magnetic fields. Here we demonstrate that step-like submicrometre topographical features can be used as reliable docking and guiding platforms for chemically active spherical Janus colloids. For various topographic features (stripes, squares or circular posts), docking of the colloid at the feature edge is robust and reliable. Furthermore, the colloids move along the edges for significantly long times, which systematically increase with fuel concentration. The observed phenomenology is qualitatively captured by a simple continuum model of self-diffusiophoresis near confining boundaries, indicating that the chemical activity and associated hydrodynamic interactions with the nearby topography are the main physical ingredients behind the observed behaviour.

JTD

Microswimmers, such as bacteria, are known to show different behaviours depending on their local environment. They identify spatial chemical gradients to find nutrient rich areas (chemotaxis) and interact with shear flows to accumulate in high shear regions. Recently, artificial microswimmers have been developed which mimic their natural counterparts in many ways. One of the exciting topics in this field is to study these artificial motors in several natural settings like the ones bacteria interact with. In this Focus article, we summarize recent observations of artificial swimmers in chemical gradients, shear flows and other interesting natural environments simulated in the lab using microfluidics and nanotechnology.

JTD

Sustainable energy generation is of recent interest due to a growing energy demand across the globe and increasing environmental issues caused by conventional non-renewable means of power generation. In the context of microsystems, portable electronics and lab-on-a-chip based (bio)chemical sensors would essentially require fully integrated, reliable means of power generation. Microfluidic-based fuel cells can offer unique advantages compared to conventional fuel cells such as high surface area-to-volume ratio, ease of integration, cost effectiveness and portability. Here, we summarize recent developments which utilize the potential of microfluidic devices for energy generation.

JTD

Soft robotics is an emerging discipline that employs soft flexible materials such as fluids, gels and elastomers in order to enhance the use of robotics in healthcare applications. Compared to their rigid counterparts, soft robotic systems have flexible and rheological properties that are closely related to biological systems, thus allowing the development of adaptive and flexible interactions with complex dynamic environments. With new technologies arising in bioengineering, the integration of living cells into soft robotic systems offers the possibility of accomplishing multiple complex functions such as sensing and actuating upon external stimuli. These emerging bio-hybrid systems are showing promising outcomes and opening up new avenues in the field of soft robotics for applications in healthcare and other fields.

JTD

The ubiquitous random motion of mesoscopic active particles, such as cells, can be “rectified” or directed by embedding the particles in systems containing local and periodic asymmetric cues. Incorporated on lab-on-a-chip devices, these microratchet-like structures can be used to self-propel fluids, transport particles, and direct cell motion in the absence of external power sources. In this Focus article we discuss recent advances in the use of ratchet-like geometries in microfluidics which could open new avenues in biomedicine for applications in diagnosis, cancer biology, and bioengineering.

JTD

Point-of-care diagnostics (PoC) and personalised medicine are highly valuable for the improvement of world health. Smartphone PoC platforms which precisely diagnose diseases and track their development through the detection of several bioanalytes represent one of the newest and most exciting advancements towards mass-screening applications. Here we focus on recent advances in both multiplexed and smartphone integrated PoC sensors.

JTD

The development of synthetic nanomotors for technological applications in particular for life science and nanomedicine is a key focus of current basic research. However, it has been challenging to make active nanosystems based on biocompatible materials consuming nontoxic fuels for providing self-propulsion. Here, we fabricate self-propelled Janus nanomotors based on hollow mesoporous silica nanoparticles (HMSNPs), which are powered by biocatalytic reactions of three different enzymes: catalase, urease, and glucose oxidase (GOx). The active motion is characterized by a mean-square displacement (MSD) analysis of optical video recordings and confirmed by dynamic light scattering (DLS) measurements. We found that the apparent diffusion coefficient was enhanced by up to 83%. In addition, using optical tweezers, we directly measured a holding force of 64 ± 16 fN, which was necessary to counteract the effective self-propulsion force generated by a single nanomotor. The successful demonstration of biocompatible enzyme-powered active nanomotors using biologically benign fuels has a great potential for future biomedical applications.

JTD Keywords: Enzyme, Hollow mesoporous silica nanoparticles, Hybrid motors, Janus particles, Nanomotors, Optical tweezers

We report on the synergy between catalytic propulsion and mesoporous silica nanoparticles (MSNPs) for the design of Janus nanomotors as active cargo delivery systems with sizes <100 nm (40, 65, and 90 nm). The Janus asymmetry of the nanomotors is given by electron beam (e-beam) deposition of a very thin platinum (2 nm) layer on MSNPs. The chemically powered Janus nanomotors present active diffusion at low H2O2 fuel concentration (i.e., <3 wt %). Their apparent diffusion coefficient is enhanced up to 100% compared to their Brownian motion. Due to their mesoporous architecture and small dimensions, they can load cargo molecules in large quantity and serve as active nanocarriers for directed cargo delivery on a chip.

JTD

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

Surface-conductive Janus spherical motors are fabricated by wrapping silica particles with reduced graphene oxide capped with a thin Pt layer. These motors exhibit a 100% enhanced velocity as compared to standard SiO2–Pt motors. Furthermore, the versatility of graphene may open up possibilities for a diverse range of applications from active drug delivery systems to water remediation.

JTD Keywords: Enhanced speed, Graphene wrapping, Janus micromotors, Janus particles, Micromotors, Surface conduction

This article will focus on recent reports that have applied three-dimensional (3D) printing for designing millimeter to micrometer architecture for robotic motility. The utilization of 3D printing has rapidly grown in applications for medical prosthetics and scaffolds for organs and tissue, but more recently has been implemented for designing mobile robotics. With an increase in the demand for devices to perform in fragile and confined biological environments, it is crucial to develop new miniaturized, biocompatible 3D systems. Fabrication of materials at different scales with different properties makes 3D printing an ideal system for creating frameworks for small-scale robotics. 3D printing has been applied for the design of externally powered, artificial microswimmers and studying their locomotive capabilities in different fluids. Printed materials have also been incorporated with motile cells for bio-hybrid robots capable of functioning by cell contraction and swimming. These 3D devices offer new methods of robotic motility for biomedical applications requiring miniature structures. Traditional 3D printing methods, where a structure is fabricated in an additive process from a digital design, and non-traditional 3D printing methods, such as lithography and molding, will be discussed.

JTD

Three-dimensional (3D) bioprinting has recently emerged as an extension of 3D material printing, by using biocompatible or cellular components to build structures in an additive, layer-by-layer methodology for encapsulation and culture of cells. These 3D systems allow for cell culture in a suspension for formation of highly organized tissue or controlled spatial orientation of cell environments. The in vitro 3D cellular environments simulate the complexity of an in vivo environment and natural extracellular matrices (ECM). This paper will focus on bioprinting utilizing hydrogels as 3D scaffolds. Hydrogels are advantageous for cell culture as they are highly permeable to cell culture media, nutrients, and waste products generated during metabolic cell processes. They have the ability to be fabricated in customized shapes with various material properties with dimensions at the micron scale. 3D hydrogels are a reliable method for biocompatible 3D printing and have applications in tissue engineering, drug screening, and organ on a chip models.

JTD

Complex-shaped microparticles (MPs) have attracted extensive interest in a myriad of scientific and engineering fields in recent years for their distinct morphology and capability in combining different functions within a single particle. Microfluidic techniques offer an intriguing method for fabricating MPs with excellent monodispersity and complex morphology in parallel while controlling their number and size precisely and independently. To date, there are two notable microfluidics approaches for the synthesis of complex-shaped MPs, namely droplet based, and flow-lithography based microfluidics approaches. It is undoubted that the application of complex-shaped MPs via microfluidic fabrication will hold great promise in a variety of fields including microfabrication, analytical chemistry and biomedicine.

JTD

The articles in this special section focus on the technologies and applications supported by micro- and nanomachines. The world of artificial micro- and nanomachines has greatly expanded over the last few years to include a range of disciplines from chemistry, physics, biology, to micro/nanoengineering, robotics, and theoretical physics. The dream of engineering nanomachines involves fabricating devices that mimic the mechanical action of biological motors that operate over multiple length scales: from molecular-scale enzymes and motors such as kinesins to the micro-scale biomachinery responsible for the motility of tiny organisms such as the flagella motors of E. coli. However, the design and fabrication of artificial nano- and micromachines with comparable performance as their biological counterparts is not a straightforward task. It requires a detailed understanding of the basic principles of the operation of biomotors and mechanisms that couple the dissipation of energy to mechanical motion. Moreover, micro engineering and microfabrication knowledge is required in order to design efficient, small and even smart micro- and nanomachines.

JTD

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

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