Self-propelled Motors Research Articles

An oral bioactive chitosan-decorated doxorubicin nanoparticles/bacteria bioconjugates enhance chemotherapy efficacy in an in-situ breast cancer model

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Despite significant advancements in chemotherapy, its effectiveness is often limited by poor drug distribution and systemic toxicity caused by the weak targeting ability of conventional therapeutic agents. The hypoxic tumor microenvironment (TME) also plays a vital role in treatment outcomes. Oral anticancer therapeutic agents have gained popularity and show promising results due to their ease of repeated administration. This study introduces autopilot biohybrids (Bif@BDC-NPs) for the effective delivery of doxorubicin (DOX) to the tumor site. This hybrid combines albumin-encapsulated DOX nanoparticles (BD-NPs) coated with chitosan (CS) for breast cancer chemotherapy, along with anaerobic Bifidobacterium infantis (B. infantis, Bif) serving as self-propelled motors. Due to Bif's specific anaerobic properties, Bif@BDC-NPs precisely anchor hypoxic regions of tumor tissue and significantly increase drug accumulation at the tumor site, thereby promoting tumor cell death. In an in-situ mouse breast cancer model, Bif@BDC-NPs achieved 94 % tumor inhibition, significantly prolonging the median survival of mice to 62 days, and reducing the toxic side effects of DOX. Therefore, the new bacteria-driven oral drug delivery system, Bif@BDC-NPs, overcomes multiple physiological barriers and holds great potential for the precise treatment of solid tumors.

A Motor-Based Carbonaceous Nanocalabash Catalyst for Deep-Layered Bioorthogonal Chemistry.

Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has been widely regarded as a promising avenue in bioorthogonal chemistry. The emerging heterogeneous copper catalysts have been developed with a series of exciting applications such as in situ activation of prodrugs because of their excellent stability and biocompatibility. However, due largely to the complex biophysical barriers in living organisms, most synthetic bioorthogonal drugs cannot penetrate deep pathological tissues. Especially in biofilm-associated infections, the biofilms severely block the penetration of traditional antimicrobial agents and increase the antibiotic resistance, which makes it extremely difficult to eliminate the biofilms. Inspired by self-propelled biological motors, such as enzymes, herein, we develop a NIR light-controllable carbonaceous nanocalabash (CNC) motor catalyst with good biocompatibility for active targeted synthesis of drugs inside the biofilms as a robust general-purpose bioorthogonal platform. Under the NIR laser, the CNC motor catalysts display a rapid autonomous motion and generate active molecules in the deep biofilm layers, removing the biofilms and eradicating the shielded bacteria. Our work will shed light on developing a robust bioorthogonal platform for active targeted synthesis of drugs in deep-layered living systems.

Non-Faradaic Electrochemical Energy Transduction Using Catalytic Motors

Mechanical energy generated by self-powered catalytic motors encourages researchers to explore whether their dynamics can be harnessed in developing inexpensive and efficient energy transduction and storage platforms. Herein, we present a non-Faradaic electrochemical energy transduction strategy using buoyancy-driven self-propelled catalytic motors within an electrochemical setup containing a fluorinated tin oxide working electrode and a sustained salt gradient. During propulsion, the motors facilitated advective transfer of ions from the bottom of the fuel solution to the electrode and subsequent formation of an electric double layer capacitor (EDLC) over it. The magnitude of EDLC charging was estimated using open circuit potential (OCP) measurements, which was found to increase with the number of motors in solution. We also observed instantaneous potential spikes over the OCP signal profile, when a motor struck the electrode surface, the frequency of which gets enhanced with the increase in motor speed through the solution. We quantify the OCP generated as a function of number of motors and composition of the fuel solution and also offer an explanation of the energy transduction mechanism in the system. It is expected that catalytic motor-assisted non-Faradaic energy generation will establish itself as an important energy harvesting pathway and when miniaturized, will open up avenues for fabricating autonomous power sources for smart sensors and other devices.

Fabrication of Pt–Ag–Au heterogeneous truncated hollow sub-microspheres for chemically self-propelled colloidal motors

Colloidal motors with cavity structure, which have advantages over solid motors in catalytic efficiency, cargo capacity and biocompatibility, are still expected. Here, we design and fabricate a type of truncated hollow sub-microsphere via organic colloidal template etching/heating and layer-by-layer isotropic deposition. The as-prepared truncated hollow sphere is of one circular open pore through the shell layer and built of Pt, Ag and Au shell layers from inside to outside. They are controllable in sphere diameter, circular open pore size and shell thickness, which depend on the template and deposition conditions. Further experiments have shown that the Ag sandwich layer and post-deposition ageing process are crucial to obtaining strong and complete truncated hollow sub-microspheres. Their formation is attributed to the template geometry and nearly isotropic deposition. Due to the catalytic Pt layer on the inner surface and the truncated hollow spherical structure, such Pt–Ag–Au hollow spheres are demonstrated to be chemically propelled colloidal motors, which can directionally move in H2O2-containing solutions. This study presents a controllable route for mass-fabricating heterogeneous multi-layer truncated hollow sub-microspheres, and provides a new type of chemically self-propelled colloidal motor.

3D inkjet printed self-propelled motors for micro-stirring

HypothesisMicroscopic self-propelled motors (SPMs) are an area of active research, but very little investigation has been conducted on millimetre-scale or macroscopic SPMs and exploring their potential in biomedical research. In this study, we tested if 3D reactive inkjet (RIJ) printing could be used for precise fabrication of millimetre-scale self-propelled motors (SPMs) with well-defined shapes from regenerated silk fibroin (RSF) by converting water soluble RSF (silk I) to insoluble silk fibroin (silk II). Secondly, we compared the different propulsion behaviour of the SPMs to put forward the best geometry and propulsion mechanism for potential applications in enhancing the sensitivity of diffusion-rate limited biomedical assays by inducing fluid flow. ExperimentsSPMs with four different geometric shapes and propelled by two different mechanisms (catalysis and surface tension gradient) were fabricated by 3D RIJ printing and compared. For bubble propulsion, the structures were selectively doped in specific regions with the enzyme catalase in order to produce motion via bubble generation and detachment in hydrogen peroxide solutions. For surface tension propulsion, PEG400-doped structures were propelled through surface tension gradients caused by leaching of PEG400 surfactant in deionized water. FindingsThe results demonstrated the ability of 3D inkjet printing to fabricate SPMs with desired propulsion mechanism and fine-tune the propulsion by precisely fabricating the different geometric shapes. The resulting 3D structures were capable of generating motion without external actuation, thereby enabling applications in biomedicine such as micro-stirring small fluid volumes to enhance biological assay sensitivity. The surface tension gradient caused by the leaching of surfactant led to faster propulsion velocities with smooth deceleration, whereas, in comparison, catalysis-induced bubble propulsion tended to be jerky and uneven in deceleration, and therefore less suitable for aforementioned applications. Computational fluid dynamic simulations were used to compare the various experimental SPMs ability to enhance mixing when deployed within 96-well plate microwells, to reveal the effect of both SPM shape and motion character on performance, and show viability for small scale mixing applications.

Self-propelled motors in complex fluids and as constituents of active materials

Simulation has played an important part in studies of active matter systems, and this paper considers some aspects of the use of stochastic models for the behavior of active particles in complex media and in applications to active functional materials. The scope of the work is primarily focused on small active particles whose activity is derived from chemical reactions and diffusiophoretic mechanisms that operate in the presence of fluctuations. Both Langevin and particle-based models are considered, and their relative merits are discussed.

Photosensitive Polymeric Janus Micromotor for Enzymatic Activity Protection and Enhanced Substrate Degradation.

Immobilizing enzymes into microcarriers is a strategy to improve their long-term stability and reusability, hindered by (UV) light irradiation. However, in such approaches, enzyme-substrate interaction is mediated by diffusion, often at slow kinetics. In contrast, enzyme-linked self-propelled motors can accelerate this interaction, frequently mediated by the convection mechanism. This work reports on a new photosensitive polymeric Janus micromotor (JM) for UV-light protection of enzymatic activity and efficient degradation of substrates accelerated by the JMs. The JMs were assembled with UV-photosensitive modified chitosan, co-encapsulating fluorescent-labeled proteins and enzymes as models and magnetite and platinum nanoparticles for magnetic and catalytic motion. The JMs absorbed UV light, protecting the enzymatic activity and accelerating the enzyme-substrate degradation by magnetic/catalytic motion. Immobilizing proteins in photosensitive JMs is a promising strategy to improve the enzyme's stability and hasten the kinetics of substrate degradation, thereby enhancing the enzymatic process's efficiency.

Reconfigurable assembly of colloidal motors towards interactive soft materials and systems

Due to the highly flexible reconfiguration of swarms, collective behaviors have provided various natural organisms with a powerful adaptivity to the complex environment. To mimic these natural systems and construct artificial intelligent soft materials, self-propelled colloidal motors that can convert diverse forms of energy into swimming-like movement in fluids afford an ideal model system at the micro-/nanoscales. Through the coupling of local gradient fields, colloidal motors driven by chemical reactions or externally physical fields can assembly into swarms with adaptivity. Here, we summarize the progress on reconfigurable assembly of colloidal motors which is driven and modulated by chemical reactions and external fields (e.g., light, ultrasonic, electric, and magnetic fields). The adaptive reconfiguration behaviors and the corresponding mechanisms are discussed in detail. The future directions and challenges are also addressed for developing colloidal motor-based interactive soft matter materials and systems with adaptation and interactive functions comparable to that of natural systems.

Autonomous Motion of Bubble-Powered Carbonaceous Nanoflask Motors.

We report a carbonaceous nanomotor with a characteristic flask-like hollow structure that can autonomously move under the propulsion of oxygen bubbles. The carbonaceous nanoflask (CNF) motor was fabricated by encapsulating platinum nanoparticles (Pt NPs) into the hollow cavity of the CNF. The internally encapsulated Pt NPs act as catalysts to decompose hydrogen peroxide (H2O2) fuel into oxygen bubbles. The generated oxygen bubbles recoil the motion of the CNF motors. Besides, the velocity of CNF motors can be controlled by adjusting the concentration of the H2O2 solution. The motion velocity increases with the increase of H2O2 concentration, up to 109.25 μm s-1 at 10% H2O2. This study provides important implications for understanding the motion behaviors of nanomotors with an internal cavity, and the self-propelled CNF motors as smart carrier systems have potential applications in the future.

Enzyme-Powered Nanomotors with Controlled Size for Biomedical Applications.

Self-propelled motors have been developed with promising potential for medical applications. However, most of them have a size range at the microscale, which limits their further research for in vivo experiments. Previously, our group developed nanoscaled motors with a size of around 400 nm with several merits, for example, delivering both hydrophobic and hydrophilic drugs/proteins, using biocompatible fuels while being able to control their motion, and showing adaptive changes of their speed and navigation to changes in the environment. It is also well-known that nanoparticles that are around 20–200 nm in size have advantages in overcoming cellular barriers and being internalized into cells. Therefore, lowering the size range of this stomatocyte nanomotor is crucial. However, the strict control of the size of vesicles in such a low regime as well as their shape transformation into folded stomatocyte structures is not trivial. In this study, we fabricated ultrasmall stomatocyte polymersomes with the size of around 150 nm, which could be a promising carrier for biomedical purposes. We demonstrated that the addition of PEG additive allows for both shape transformation of small polymersomes into stomatocytes and encapsulation of biologics. Biocatalyst catalase was encapsulated in the inner compartment of the nanomotor, protecting the enzyme while providing enough thrust to propel the motors. The ultrasmall stomatocyte motor system allowed propelled motion by converting H2O2 into O2 in the presence of only 2 mM H2O2, and the velocity of motors correlated to the O2 production. Compared to small stomatocyte nanomotors, ultrasmall stomatocyte motors demonstrate enhanced penetration across the vasculature model and increased uptake by HeLa cells in the presence of fuel.

Multifunctional and biodegradable self-propelled protein motors

A diversity of self-propelled chemical motors, based on Marangoni propulsive forces, has been developed in recent years. However, most motors are non-functional due to poor performance, a lack of control, and the use of toxic materials. To overcome these limitations, we have developed multifunctional and biodegradable self-propelled motors from squid-derived proteins and an anesthetic metabolite. The protein motors surpass previous reports in performance output and efficiency by several orders of magnitude, and they offer control of their propulsion modes, speed, mobility lifetime, and directionality by regulating the protein nanostructure via local and external stimuli, resulting in programmable and complex locomotion. We demonstrate diverse functionalities of these motors in environmental remediation, microrobot powering, and cargo delivery applications. These versatile and degradable protein motors enable design, control, and actuation strategies in microrobotics as modular propulsion sources for autonomous minimally invasive medical operations in biological environments with air-liquid interfaces.

Biocatalytic self-propelled submarine-like metal-organic framework microparticles with pH-triggered buoyancy control for directional vertical motion

Self-propelled submarine-like microparticles that can exploit buoyancy force for directional vertical motion is reported. A slight shift in pH can cause the generated gas bubbles to be reversibly retained/expelled from the micromotor particles, leading to the buoyancy-directed vertical motion with speed regulation. This study will open up new avenues for designing directional propulsion mechanisms for chemical motors and robotics, showing potential as smart cargo transport microsystems that are sensitive to their environment. Self-propelled chemical motors have found vast promise for applications from nanomedicine to environmental remediation. However, strategies for controlling their directional motion on demand still represents one of the major challenges for the development of smart motor systems to be realized in real-world applications. Here, we report for the first time the design of a novel submarine-like micromotor that is capable of directional vertical motion on centimeter scale by pH-regulated buoyancy control. With the aid of a pH-responsive, hydrophilic/hydrophobic phase-shifting polymer, gas bubbles produced by the biocatalytic metal–organic framework micromotors can be reversibly retained/expelled from the micromotors, leading to the buoyancy-controlled ascending or descending vertical motion. Importantly, anti-cancer drug-loaded micromotors showed directional cytotoxicity to three-dimensional cell cultures, depending on the pH of the cellular environment. We expect this study will open up new avenues for designing directional propulsion mechanisms for chemical motors, showing potential as autonomous robotics for in vivo delivery in complex biological environments.

Diffusion Measurements of Swimming Enzymes with Fluorescence Correlation Spectroscopy.

Self-propelled chemical motors are chemically powered micro- or nanosized swimmers. The energy required for these motors' active motion derives from catalytic chemical reactions and the transformation of a fuel dissolved in the solution. While self-propulsion is now well established for larger particles, it is still unclear if enzymes, nature's nanometer-sized catalysts, are potentially also self-powered nanomotors. Because of its small size, any increase in an enzyme's diffusion due to active self-propulsion must be observed on top of the enzyme's passive Brownian motion, which dominates at this scale. Fluorescence correlation spectroscopy (FCS) is a sensitive method to quantify the diffusion properties of single fluorescently labeled molecules in solution. FCS experiments have shown a general increase in the diffusion constant of a number of enzymes when the enzyme is catalytically active. Diffusion enhancements after addition of the enzyme's substrate (and sometimes its inhibitor) of up to 80% have been reported, which is at least 1 order of magnitude higher than what theory would predict. However, many factors contribute to the FCS signal and in particular the shape of the autocorrelation function, which underlies diffusion measurements by fluorescence correlation spectroscopy. These effects need to be considered to establish if and by how much the catalytic activity changes an enzyme's diffusion. We carefully review phenomena that can play a role in FCS experiments and the determination of enzyme diffusion, including the dissociation of enzyme oligomers upon interaction with the substrate, surface binding of the enzyme to glass during the experiment, conformational changes upon binding, and quenching of the fluorophore. We show that these effects can cause changes in the FCS signal that behave similar to an increase in diffusion. However, in the case of the enzymes F1-ATPase and alkaline phosphatase, we demonstrate that there is no measurable increase in enzyme diffusion. Rather, dissociation and conformational changes account for the changes in the FCS signal in the former and fluorophore quenching in the latter. Within the experimental accuracy of our FCS measurements, we do not observe any change in diffusion due to activity for the enzymes we have investigated. We suggest useful control experiments and additional tests for future FCS experiments that should help establish if the observed diffusion enhancement is real or if it is due to an experimental or data analysis artifact. We show that fluorescence lifetime and mean intensity measurements are essential in order to identify the nature of the observed changes in the autocorrelation function. While it is clear from theory that chemically active enzymes should also act as self-propelled nanomotors, our FCS measurements show that the associated increase in diffusion is much smaller than previously reported. Further experiments are needed to quantify the contribution of the enzymes' catalytic activity to their self-propulsion. We hope that our findings help to establish a useful protocol for future FCS studies in this field and help establish by how much the diffusion of an enzyme is enhanced through catalytic activity.

Self-Propelled Nanomotors for Thermomechanically Percolating Cell Membranes.

We report a near-infrared (NIR) light-powered Janus mesoporous silica nanomotor (JMSNM) with macrophage cell membrane (MPCM) cloaking that can actively seek cancer cells and thermomechanically percolate cell membrane. Upon exposure to NIR light, a heat gradient across the Janus boundary of the JMSNMs is generated by the photothermal effect of the Au half-shells, resulting in a self-thermophoretic force that propels the JMSNMs. In biological medium, the MPCM camouflaging can not only prevent dissociative biological blocks from adhering to JMSNMs but also improve the seeking sensitivity of the nanomotors by specifically recognizing cancer cells. The biofriendly propulsion and recognition capability enable JMSNMs to achieve the active seeking and bind to the membrane of cancer cells. Subsequent illumination with NIR then triggers the photothermal effect of MPCM@JMSNMs to thermomechanically perforate the cytomembranes for guest molecular injection. This approach integrates the functions of active seeking, cytomembranes perforating, and thermomechanical therapy in nanomotors, which may pave the way to apply self-propelled motors in biomedical fields.

Mini-EmulsionFabricated Magnetic and Fluorescent Hybrid Janus Micro-Motors.

Self-propelling micro/nano-motors have attracted great attention due to their controllable active motion and various functional attributes. To date, a variety of technologies have been reported for the fabrication of micro/nano-motors. However, there are still several challenges that need to be addressed. One of them is to endow micro/nano-motors with multi-functionalities by a facile fabrication process. Here, we present a universal approach, adopted from the emulsion templating method, for the fabrication of Janus micro-motors. With a one-step process, magnetic nanoparticles and fluorescent dyes are simultaneously embedded into the microparticles. The self-propelled motors can be used as an active label or fluorescent tracer through manipulation of their motion using magnetic guidance.

Nanoscale active matter matters: Challenges and opportunities for self-propelled nanomotors

Progress in nanotechnology has enabled the synthesis of active particles that can harness chemical energy and translate it into useful work. Catalytic self-propelled motors have implications for understanding out-of-equilibrium systems and have potential applications in active transport at the nanoscale, where they can be used as motors and pumps. Although much research has been done on micron-sized motors, progress in catalytic nanomotors of sub 100 nm is still in its infancy. These nanosized motors are of great importance for future molecular transport at the cellular level because they operate at length scales at which protein motors work. This opinion article focusses on recent advances in the synthesis of catalytic nanomotors and experimental strategies to measure their self-propulsion, which differ from that of micromotors. Enzymatic and metallic nanomotors are surveyed, together with various theoretical models for self-propulsion. Solutions to current challenges are proposed, which include a chemical synthesis approach, new characterisation of motor activity and potential uses of nanomotors in nanomedicine.

Chemotactic and hydrodynamic effects on collective dynamics of self-diffusiophoretic Janus motors

Collective motion in nonequilibrium steady state suspensions of self-propelled Janus motors driven by chemical reactions can arise due to interactions coming from direct intermolecular forces, hydrodynamic flow effects, or chemotactic effects mediated by chemical gradients. The relative importance of these interactions depends on the reactive characteristics of the motors, the way in which the system is maintained in a steady state, and properties of the suspension, such as the volume fraction. From simulations of a microscopic hard collision model for the interaction of fluid particles with the Janus motor we show that dynamic cluster states exist and determine the interaction mechanisms that are responsible for their formation. The relative importance of chemotactic and hydrodynamic effects is identified by considering a microscopic model in which chemotactic effects are turned off while the full hydrodynamic interactions are retained. The system is maintained in a steady state by means of a bulk reaction in which product particles are reconverted into fuel particles. The influence of the bulk reaction rate on the collective dynamics is also studied.

Controlled molecular assembly of self-propelled colloid motors and their biomedical applications

Synthetic colloid motors are the micro-/nanomachines which can harvest different types of energies into mechanical motion in the fluids. Since 2012, it has been one of important strategies for controlled fabrication of colloidal motors to combine effectively controlled molecular assembly (“bottom up”) with top-down approaches. Colloid motors based on controllable molecular assembly possess the advantages of: (1) mass production, (2) response to the external stimuli, and (3) access to multifunctionality. This review will summarize the progress on the controlled preparation, motion control, and biomedical applications of colloid motors through integrating multifunctional building blocks into assemblies. This review will also introduce the controlled preparation of bubble-propelled colloid motors based on layer-by-layer assembled microcapsules, nanotubes, shells, and two-dimensional plates, the fabrication of near-infrared-light-driven colloidal motors based on polyelectrolytic multilayer microcapsules and nanotubes, the controlled fabrication of biointerfacing colloidal motors, the effective control over the movement speeds, directions, and states of motors through integrating functional components, and the applications of motors in biomedical fields including drug targeted delivery, photothermal therapy, and biodetoxification.

Self-propelled motors: Light-seeking synthetic trees.

Nanostructured photocatalytic microrods can swim either towards or away from a light source depending on their surface functionalization.

Enzyme Catalysis To Power Micro/Nanomachines.

Enzymes play a crucial role in many biological processes which require harnessing and converting free chemical energy into kinetic forces in order to accomplish tasks. Enzymes are considered to be molecular machines, not only because of their capability of energy conversion in biological systems but also because enzymatic catalysis can result in enhanced diffusion of enzymes at a molecular level. Enlightened by nature’s design of biological machinery, researchers have investigated various types of synthetic micro/nanomachines by using enzymatic reactions to achieve self-propulsion of micro/nanoarchitectures. Yet, the mechanism of motion is still under debate in current literature. Versatile proof-of-concept applications of these enzyme-powered micro/nanodevices have been recently demonstrated. In this review, we focus on discussing enzymes not only as stochastic swimmers but also as nanoengines to power self-propelled synthetic motors. We present an overview on different enzyme-powered micro/nanomachines, the current debate on their motion mechanism, methods to provide motion and speed control, and an outlook of the future potentials of this multidisciplinary field.