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.     

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。     

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.     

Motion Control of Micro‐/Nanomotors

As we progress towards employing self‐propelled micro‐/nanomotors in envisioned applications such as cargo delivery, environmental remediation, and therapeutic treatments, precise control of the micro‐/nanomotors direction and their speed is essential. In this Review, major emerging approaches utilized for the motion control of micro‐/nanomotors have been discussed, together with the lastest publications describing these approaches. Future studies could incorporate investigations on micro‐/nanomotors motion control in a real‐world environment in which matrix complexity might disrupt successful manipulation of these small‐scale devices.     

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.     

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.     

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.     

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.     

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.     

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.     

Chemical‐Template Synthesis of Micro/Nanoscale Magnesium Silicate Hollow Spheres for Waste‐Water Treatment

Micro/nanoscale magnesium silicate hollow spheres were synthesized by using silica colloidal spheres as a chemical template in one pot. The hollow spherical structure, consisting of well‐separated nanoscale units, was microscale as a whole and could be easily handled in solution. The as‐synthesized magnesium silicate hollow spheres with large specific surface area showed availability for the removal of organic and heavy‐metal ions efficiently from waste water. Importantly, the micro/nanoscale magnesium silicate hollow spheres that had adsorbed organic pollutants could be regenerated by calcination and used repeatedly in pollutant removal. Magnesium silicate hollow spheres synthesized by a scaled‐up chemical template method may have potential applications in removing cationic dyes and heavy‐metal ions from waste water.     

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.     

Acoustic Propulsion of Nanorod Motors Inside Living Cells

The ultrasonic propulsion of rod‐shaped nanomotors inside living HeLa cells is demonstrated. These nanomotors (gold rods about 300 nm in diameter and about 3 μm long) attach strongly to the external surface of the cells, and are readily internalized by incubation with the cells for periods longer than 24 h. Once inside the cells, the nanorod motors can be activated by resonant ultrasound operating at 4 MHz, and show axial propulsion as well as spinning. The intracellular propulsion does not involve chemical fuels or high‐power ultrasound and the HeLa cells remain viable. Ultrasonic propulsion of nanomotors may thus provide a new tool for probing the response of living cells to internal mechanical excitation, for controllably manipulating intracellular organelles, and for biomedical applications.     

Motion-driven sensing and biosensing using electrochemically propelled nanomotors

Electrochemically-propelled nanomotors offer considerable promise for developing new and novel bioanalytical and biosensing strategies based on the direct isolation of target biomolecules or changes in their movement in the presence of target analytes. For example, receptor-functionalized nanomotors offer direct and rapid target isolation from raw biological samples without preparatory and washing steps. Microtube engines functionalized with ss-DNA, aptamer or antibody receptors are particularly useful for the direct isolation of nucleic acids, proteins or cancer cells, respectively. A new nanomotor-based signal transduction involving measurement of speed and distance travelled by nanomotors, offers highly sensitive, rapid, simple and low cost detection of target biomarkers, and a new dimension of analytical information based on motion. The resulting distance signals can be easily visualized by optical microscope (without any sophisticated analytical instrument) to reveal the target presence and concentration. The attractive features of the new micromachine-based target isolation and signal transduction protocols reviewed in this article offer numerous potential applications in biomedical diagnostics, environmental monitoring, and forensic analysis.     

Self-Propelling Hybrid Gels Incorporating an Active Self-Assembled,Low-Molecular-Weight Gelator

Hybrid gel beads based on combining a low-molecular-weight gelator (LMWG) with a polymer gelator (PG) demonstrate an enhanced ability to self-propel in water, with the LMWG playing an active role. Hybrid gel beads were loaded with ethanol and shown to move in water owing to the Marangoni effect changes in surface tension caused by the expulsion of ethanol – smaller beads move farther and faster than larger beads. Flat shapes of the hybrid gel were cut using a “stamp” – circles moved the furthest, whereas stars showed more rotation on their own axes. Comparing hybrid LMWG/PG gel beads with PG-only beads demonstrated that the LMWG speeds up the beads, enhancing the rate of self-propulsion. Self-assembly of the LMWG into a “solid-like” network prevents its leaching from the gel. The LMWG also retains its own unique function – specifically, remediating methylene blue pollutant dye from basic water as a result of noncovalent interactions. The mobile hybrid beads accumulate this dye more effectively than PG-only beads. Self-propelling gel beads have potential applications in removal/delivery of active agents in environmental or biological settings. The ability of self-assembling LMWGs to enhance mobility and control removal/delivery suggests that adding them to self-propelling systems can add significant value.     

Salt‐Induced Fabrication of Superhydrophilic and Underwater Superoleophobic PAA‐g‐PVDF Membranes for Effective Separation of Oil‐in‐Water Emulsions

Conventional polymer membranes suffer from low flux and serious fouling when used for treating emulsified oil/water mixtures. Reported herein is the fabrication of a novel superhydrophilic and underwater superoleophobic poly(acrylic acid)‐grafted PVDF filtration membrane using a salt‐induced phase‐inversion approach. A hierarchical micro/nanoscale structure is constructed on the membrane surface and endows it with a superhydrophilic/underwater superoleophobic property. The membrane separates both surfactant‐free and surfactant‐stabilized oil‐in‐water emulsions under either a small applied pressure (<0.3 bar) or gravity, with high separation efficiency and high flux, which is one to two orders of magnitude higher than those of commercial filtration membranes having a similar permeation property. The membrane exhibits an excellent antifouling property and is easily recycled for long‐term use. The outstanding performance of the membrane and the efficient, energy and cost‐effective preparation process highlight its potential for practical applications.     

Biocatalytic Micro- and Nanomotors

Enzyme-powered micro- and nanomotors are tiny devices inspired by nature that utilize enzyme-triggered chemical conversion to release energy stored in the chemical bonds of a substrate (fuel) to actuate it into active motion. Compared with conventional chemical micro-/nanomotors, these devices are particularly attractive because they self-propel by utilizing biocompatible fuels, such as glucose, urea, glycerides, and peptides. They have been designed with functional material constituents to efficiently perform tasks related to active targeting, drug delivery and release, biosensing, water remediation, and environmental monitoring. Because only a small number of enzymes have been exploited as bioengines to date, a new generation of multifunctional, enzyme-powered nanorobots will emerge in the near future to selectively search for and utilize water contaminants or disease-related metabolites as fuels. This Minireview highlights recent progress in enzyme-powered micro- and nanomachines.     

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.     

Fabrication and Manipulation of Magnetic Composite Particles with Specific Shape and Size

The fabrication of microscale polyethylene glycol diacrylate(PEGDA) hydrogel particles was demonstrated via magnetic property ultraviolet(UV) lithography techniques, polydimethylsiloxane(PDMS) soft stamp pre-paration techniques and micro-nano imprint technology in this paper. The results of compositional and morphological characterizations of magnetic microparticles show that the Fe₃O₄ nanoparticles with an average diameter of 100 nm are uniformly dispersed in hydrogel. Owing to the excellent magnetism of Fe₃O₄ nanoparticles, the fabricated hydrogel microparticles with different sizes and shapes were manipulated in water via applying an external magnetic fields. Three types of motions, translation, rotation and flip, were demonstrated with the manipulator. These microscale magnetic PEGDA hydrogel particles have a great application potential in manufacturing process, micro/nanomotors, and machines.