Fuel‐Free Micro‐/Nanomotors as Intelligent Therapeutic Agents

There are many efficient biological motors in Nature that perform complex functions by converting chemical energy into mechanical motion. Inspired by this, the development of their synthetic counterparts has aroused tremendous research interest in the past decade. Among these man‐made motor systems, the fuel‐free (or light, magnet, ultrasound, or electric field driven) motors are advantageous in terms of controllability, lifespan, and biocompatibility concerning bioapplications, when compared with their chemically powered counterparts. Therefore, this review will highlight the latest biomedical applications in the versatile field of externally propelled micro‐/nanomotors, as well as elucidating their driving mechanisms. A perspective into the future of the micro‐/nanomotors field and a discussion of the challenges we need to face along the road towards practical clinical translation of external‐field‐propelled micro‐/nanomotors will be provided.     

Chemically Powered Micro‐ and Nanomotors

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.     

Design and Fabrication of Tubular Micro/Nanomotors via 3D Laser Lithography

Catalytic tubular micro/nanomachines convert chemical energy from a surrounding aqueous fuel solution into mechanical energy to generate autonomous movements, propelled by the oxygen bubbles decomposed by hydrogen peroxide and expelled from the microtubular cavity. With the development of nanotechnology, micro/nanomotors have attracted more and more interest due to their numerous potential for in vivo and in vitro applications. Here, highly efficient chemical catalytic microtubular motors were fabricated via 3D laser lithography and their motion behavior under the action of driving force in fluids was demonstrated. The frequency of catalytically‐generated bubbles ejection was influenced by the geometrical shape of the micro/nanomotor and surrounding chemical fuel environment, resulting in the variation in motion speed. The micro/nanomotors generated with a rocket‐like shape displayed a more active motion compared with that of a single tubular micro/nanomotor, providing a wider range of practical micro‐/nanoscale applications in the future.     

One Modification,Two Functions: Single Ni‐modified Light‐Driven ZnO Microrockets with Both Efficient Propulsion and Steerable Motion

Efficient propulsion and effective direction control are essential for self‐propelled micro/nanomotors. Here, a new “two‐in‐one” strategy for making attractive light‐driven micro/nanomotors is demonstrated. We make use of the metallic and magnetic properties of low‐cost Ni and incorporate just a single Ni layer into ZnO‐based microrockets, so that the resulting ZnO‐Ni microrockets can be both efficiently propelled by low energy (low light intensities and fuel concentrations) and effectively steered by a magnetic field. This successful demonstration of ZnO‐Ni microrockets is significant for the development of highly efficient synthetic micro/nanomotors, which have strong delivery ability and efficient direction control for future applications across the micro/nanoscale field.     

Motion Control of Polymeric Nanomotors Based on Host–Guest Interactions

Controlling the motion of artificial self‐propelled micro‐ and nanomotors independent of the fuel concentration is still a great challenge. Here we describe the first report of speed manipulation of supramolecular nanomotors via blue light‐responsive valves, which can regulate the access of hydrogen peroxide fuel into the motors. Light‐sensitive polymeric nanomotors are built up via the self‐assembly of functional block copolymers, followed by bowl‐shaped stomatocyte formation and incorporation of platinum nanoparticles. Subsequent addition of β‐cyclodextrin (β‐CD) leads to the formation of inclusion complexes with the trans‐isomers of the azobenzene derivatives grafted from the surfaces of the stomatocytes. β‐CDs attachment decreases the diffusion rate of hydrogen peroxide into the cavities of the motors because of partly blocking of the openings of the stomatocyte. This results in a lowering of the speed of the nanomotors. Upon blue light irradiation, the trans‐azobenzene moieties isomerize to the cis‐form, which lead to the detachment of the β‐CDs due to their inability to form complexes with the cis‐isomer. As a result, the speed of the nanomotors increases accordingly. Such a conformational change provides us with the unique possibility to control the speed of the supramolecular nanomotor via light‐responsive host–guest complexation. We envision that such artificial responsive nano‐systems with controlled motion could have potential applications in drug delivery.     

Micro/Nanomotors for Water Purification

Self-propelled micro/nanomotors are synthetic machines that can convert different sources of energy into motion; at the same time, they are able to serve innovative environmental applications, for example, water purification. The self-propelled micro and nanomachines can rapidly zoom through the solution, carrying catalytic surface or chemical to remove or degrade pollutants in a much faster fashion than that of static systems, which depend on diffusion and fluxes. This review highlights the recent progress of micro/nanomotors in water pollutant detection and pollutant removal applications.     

Achieving Control in Micro-/Nanomotor Mobility

Unprecedented opportunities exist for the generation of advanced nanotechnologies based on synthetic micro/nanomotors (MNMs), such as active transport of medical agents or the removal of pollutants. In this regard, great efforts have been dedicated toward controlling MNM motion (e.g., speed, directionality). This was generally performed by precise engineering and optimizing of the motors′ chassis, engine, powering mode (i.e., chemical or physical), and mechanism of motion. Recently, new insights have emerged to control motors mobility, mainly by the inclusion of different modes that drive propulsion. With high degree of synchronization, these modes work providing the required level of control. In this Minireview, we discuss the diverse factors that impact motion; these include MNM morphology, modes of mobility, and how control over motion was achieved. Moreover, we highlight the main limitations that need to be overcome so that such motion control can be translated into real applications.     

面向疾病应用的微纳米马达

微纳米马达是能将环境中的化学反应或外场(光、声、磁场、电场等)提供的能量转化为推进力,从而产生自主运动的微纳米级人造机器。由于具有集群效应、比表面积大、运动可控等多种特征,微纳米马达在环境修复、药物递送、微纳手术、抗感染、重金属清除等诸多领域受到关注。在一定条件下,微纳米马达能主动运动并聚集到病灶,将治疗或诊断药物递送到靶部位,有望在人体复杂环境中进行精细化的工作。因此,微纳米马达在疾病预防、诊断、治疗以及预后中具有巨大的发展空间。在此,本综述首先对微纳米马达进行简要介绍,包括其结构设计、驱动方式。其次,详细介绍微纳米马达在不同类型的疾病中的研究进展。最后,提出目前该技术面临的挑战与未来发展方向。     

Enzyme Conformation Influences the Performance of Lipase-powered Nanomotors

Enzyme-powered micro/nanomotors have myriads of potential applications in various areas. To efficiently reach those applications, it is necessary and critical to understand the fundamental aspects affecting the motion dynamics. Herein, we explored the impact of enzyme orientation on the performance of lipase-powered nanomotors by tuning the lipase immobilization strategies. The influence of the lipase orientation and lid conformation on substrate binding and catalysis was analyzed using molecular dynamics simulations. Besides, the motion performance indicates that the hydrophobic binding (via OTES) represents the best orienting strategy, providing 48.4 % and 95.4 % increase in diffusion coefficient compared to hydrophilic binding (via APTES) and Brownian motion (no fuel), respectively (with C_[triacetin] of 100 mm ). This work provides vital evidence for the importance of immobilization strategy and corresponding enzyme orientation for the catalytic activity and in turn, the motion performance of nanomotors, and is thus helpful to future applications.     

Continuously Variable Regulation of the Speed of Bubble‐Propelled Janus Microcapsule Motors Based on Salt‐Responsive Polyelectrolyte Brushes

The engineering of self‐propelled micro‐/nanomotors (MNMs) with continuously variable speeds, akin to macroscopic automobiles equipped with a continuously variable transmission, is still a huge challenge. Herein, after grafting with salt‐responsive poly[2‐(methacryloyloxy)ethyltrimethylammonium chloride] (PMETAC) brushes, bubble‐propelled Janus microcapsule motors with polyelectrolyte multilayers exhibited adjustable speeds when the type and concentration of the counterion was changed. Reversible switching between low‐ and high‐speed states was achieved by modulating the PMETAC brushes between hydrophobic and hydrophilic configurations by ion exchange with ClO₄^? and polyphosphate anions. This continuously variable regulation enabled control of the speed in an accurate and predictable manner and an autonomous response to the local chemical environment. This study suggests that the integration of polymer brushes with precisely adjustable responsiveness offers a promising route for motion control of smart MNMs that act like their counterparts in living systems.     

Photocatalytically Powered Matchlike Nanomotor for Light‐Guided Active SERS Sensing

Surface enhanced Raman spectroscopy (SERS) is a powerful optical sensing technique that can detect analytes of extremely low concentrations. However, the presence of enough SERS probes in the detection area and a close contact between analytes and SERS probes are critical for efficient acquisition of a SERS signal. Presented here is a light‐powered micro/nanomotor (MNM) that can serve as an active SERS probe. The matchlike AgNW@SiO₂ core–shell structure of the nanomotors work as SERS probes based on the shell‐isolated enhanced Raman mechanism. The AgCl tail serves as photocatalytic nanoengine, providing a self‐propulsion force by light‐induced self‐diffusiophoresis. The phototactic behavior was utilized to achieve enrichment of the nanomotor‐based SERS probes for on‐demand biochemical sensing. The results demonstrate the possibility of using photocatalytic nanomotors as active SERS probes for remote, light‐controlled, and smart biochemical sensing on the micro/nanoscale.     

Systematic Research and Evaluation Models of Nanomotors for Cancer Combined Therapy

Limited tumor permeability of therapeutic agents is a great challenge faced by current cancer therapy methods. Herein, a kind of near infrared light (NIR)‐driven nanomotor with autonomous movement, targeted ability, hierarchical porous structure, multi‐drugs for cancer chemo/photothermal therapy is designed, prepared and characterized. Further, we establish a method to study the interaction between nanomotors and cells, along with their tumor permeability mechanism, including 2D cellular models, 3D multicellular tumor spheroids and in vivo models. In vivo tumor elimination results verify that the movement behaviour of the nanomotors can greatly facilitate them to eliminate tumor through multiple therapeutic methods. This work tries to establish systematic research and evaluation models, providing strategies to understand the relationship between motion behaviour and tumor permeation efficiency of nanomotors in depth.     

Redox‐Sensitive Stomatocyte Nanomotors: Destruction and Drug Release in the Presence of Glutathione

The development of artificial nanomotor systems that are stimuli‐responsive is still posing many challenges. Herein, we demonstrate the self‐assembly of a redox‐responsive stomatocyte nanomotor system, which can be used for triggered drug release under biological reducing conditions. The redox sensitivity was introduced by incorporating a disulfide bridge between the hydrophilic poly(ethylene glycol) block and the hydrophobic polystyrene block. When incubated with the endogenous reducing agent glutathione at a concentration comparable to that within cells, the external PEG shells of these stimuli‐responsive nanomotors are cleaved. The specific bowl‐shaped stomatocytes aggregate after the treatment with glutathione, leading to the loss of motion and triggered drug release. These novel redox‐responsive nanomotors can not only be used for remote transport but also for drug delivery, which is promising for future biomedical applications.     

Microfluidic Lithography of Bioinspired Helical Micromotors

Considerable efforts have been devoted to developing artificial micro/nanomotors that can convert energy into movement. A flow lithography integrated microfluidic spinning and spiraling system is developed for the continuous generation of bioinspired helical micromotors. Because the generation processes could be precisely tuned by adjusting the flow rates and the illuminating frequency, the length, diameter, and pitch of the helical micromotors were highly controllable. Benefiting from the fast online gelation and polymerization, the resultant helical micromotors could be imparted with Janus, triplex, and core–shell cross‐sectional structures that have never been achieved by other methods. Owing to the spatially controlled encapsulation of functional nanoparticles in the microstructures, the helical micromotors can perform locomotion not only by magnetically actuated rotation or corkscrew motion but also through chemically powered catalytic reaction.     

Turn‐Number‐Dependent Motion Behavior of Catalytic Helical Carbon Micro/Nanomotors

Helical micro/nanomotors (MNMs) can be propelled by external fields to swim through highly viscous fluids like complex biological environments, which promises miniaturized robotic tools to perform assigned tasks at small scales. However, the catalytic propulsion method, most widely adopted to drive MNMs, is seldom studied to actuate helical MNMs. Herein, we report catalytic helical carbon MNMs (CHCM) by sputtering Pt onto helical carbon nano‐coils (HCNC) that are in bulk prepared by a thermal chemical vapor deposition method. The Pt‐triggered H₂O₂ decomposition can drive the MNMs by an electrokinetic mechanism. The MNMs demonstrate versatile motion behaviors including both directional propulsion and rotation depending on the turn number of the carbon helix. Besides, due to the ease of surface functionalization on carbon and other properties such as biocompatibility and photothermal effect, the helical carbon MNMs promise multifunctional applications for biomedical or environmental applications.     

Thermoresponsive Polymer Brush Modulation on the Direction of Motion of Phoretically Driven Janus Micromotors

We report a thermoresponsive poly(N‐isopropylacrylamide) (PNIPAM) brush functionalized Janus Au–Pt bimetallic micromotor capable of modulating the direction of motion with the change of the ambient temperature. The PNIPAM@Au–Pt micromotor moved along the Au–Pt direction with a speed of 8.5 μm s^?1 in 1.5 % H₂O₂ at 25 °C (below the lower critical solution temperature (LCST) of PNIPAM), whereas it changed the direction of motion (i.e., along the Pt–Au direction) and the speed decreased to 2.3 μm s^?1 at 35 °C (above LCST). Below LCST, PNIPAM brushes grafted on the Au side were hydrophilic and swelled, which permitted the electron transfer and proton diffusion on the Au side, and thus the motion is regarded as a self‐electrophoretic mechanism. However, PNIPAM brushes above LCST became hydrophobic and collapsed, and thus the driving mechanism switched to the self‐diffusiophoresis like that of Pt‐modified Janus silica motors. These motors could reversibly change the direction of motion with the transition of the hydrophobic and hydrophilic states of the grafted PNIPAM brushes. Such a thermoresponsive polymer brush functionalization method provides a new strategy for engineering the kinematic behavior of phoretically driven micro/nanomotors.     

Cargo-towing synthetic nanomachines: towards active transport in microchip devices

This review article discusses the use of synthetic catalytic nano motors for cargo manipulations and for developing miniaturized lab-on-chip systems based on autonomous transport. The ability of using chemically-powered artificial nanomotors to capture, transport and release therapeutic payloads or nanostructured biomaterials represents one of the next major prospects for nanomotor development. The increased cargo-towing force of such self-propelled nanomotors, along with their precise motion control within microchannel networks, versatility and facile functionalization, pave the way to new integrated functional lab-on-a-chip powered by active transport and perform a series of tasks. Such use of cargo-towing artificial nanomotors has been inspired by on-chip kinesin molecular shuttles. Functionalized nano/microscale motors can thus be used to pick a selected nano/microscale chemical or biological payload target at the right place, transport and deliver them to a target location in a timely manner. Key challenges for using synthetic nanomachines for driving transport processes along microchannel networks are discussed, including loading and unloading of cargo and precise motion control, along with recent examples of related cargo manipulation processes and guided transport in lab-on-a-chip formats. The exciting research area of cargo-carrying catalytic man-made nanomachines is expected to grow rapidly, to lead to new lab-on-a-chip formats and to provide a wide range of future microchip opportunities.     

Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound‐Propelled Nanomotors

Direct and rapid intracellular delivery of a functional Cas9/sgRNA complex using ultrasound‐powered nanomotors is reported. The Cas9/sgRNA complex is loaded onto the nanomotor surface through a reversible disulfide linkage. A 5 min ultrasound treatment enables the Cas9/sgRNA‐loaded nanomotors to directly penetrate through the plasma membrane of GFP‐expressing B16F10 cells. The Cas9/sgRNA is released inside the cells to achieve highly effective GFP gene knockout. The acoustic Cas9/sgRNA‐loaded nanomotors display more than 80 % GFP knockout within 2 h of cell incubation compared to 30 % knockout using static nanowires. More impressively, the nanomotors enable highly efficient knockout with just 0.6 nm of the Cas9/sgRNA complex. This nanomotor‐based intracellular delivery method thus offers an attractive route to overcome physiological barriers for intracellular delivery of functional proteins and RNAs, thus indicating considerable promise for highly efficient therapeutic applications.     

The Application of Micro‐ and Nanomotors in Classified Drug Delivery

Micro and nanomotors (MNMs) are micro/nanoscale devices that are able to convert chemical or external energy into mechanical motion. Based on a multitude of propulsion mechanisms, synthetic MNMs have been developed over the past decades for diverse biomedical applications, particularly drug delivery. Herein, we set out the classification of drugs delivered by MNMs, such as small molecules, nucleic acid, peptides, antibodies, and other proteins, and discuss their current limitations and possibilities in in vivo applications. Challenges and future perspectives are also discussed. With the increasing research enthusiasm in this field and the strengthening of multidisciplinary cooperation, intelligent MNMs will appear in the near future, which will have a profound impact on all related fields.     

Tunable DNA Origami Motors Translocate Ballistically Over μm Distances at nm/s Speeds

Inspired by biological motor proteins, that efficiently convert chemical fuel to unidirectional motion, there has been considerable interest in developing synthetic analogues. Among the synthetic motors created thus far, DNA motors that undertake discrete steps on RNA tracks have shown the greatest promise. Nonetheless, DNA nanomotors lack intrinsic directionality, are low speed and take a limited number of steps prior to stalling or dissociation. Herein, we report the first example of a highly tunable DNA origami motor that moves linearly over micron distances at an average speed of 40 nm/min. Importantly, nanomotors move unidirectionally without intervention through an external force field or a patterned track. Because DNA origami enables precise testing of nanoscale structure‐function relationships, we were able to experimentally study the role of motor shape, chassis flexibility, leg distribution, and total number of legs in tuning performance. An anisotropic rigid chassis coupled with a high density of legs maximizes nanomotor speed and endurance.