Micro‐/Nanomotors toward Biomedical Applications: The Recent Progress in Biocompatibility

Inspired by the highly versatile natural motors, artificial micro‐/nanomotors that can convert surrounding energies into mechanical motion and accomplish multiple tasks are devised. In the past few years, micro‐/nanomotors have demonstrated significant potential in biomedicine. However, the practical biomedical applications of these small‐scale devices are still at an infant stage. For successful bench‐to‐bed translation, biocompatibility of micro‐/nanomotor systems is the central issue to be considered. Herein, the recent progress in micro‐/nanomotors in biocompatibility is reviewed, with a special focus on their biomedical applications. Through close collaboration between researches in the nanoengineering, material chemistry, and biomedical fields, it is expected that a promising real‐world application platform based on micro‐/nanomotors will emerge in the near future.     

Motion Manipulation of Micro‐ and Nanomotors

Inspired by the self‐migration of microorganisms in nature, artificial micro‐ and nanomotors can mimic this fantastic behavior by converting chemical fuel or external energy into mechanical motion. These self‐propelled micro‐ and nanomotors, designed either by top‐down or bottom‐up approaches, are able to achieve different applications, such as environmental remediation, sensing, cargo/sperm transportation, drug delivery, and even precision micro‐/nanosurgery. For these various applications, especially biomedical applications, regulating on‐demand the motion of micro‐ and nanomotors is quite essential. However, it remains a continuing challenge to increase the controllability over motors themselves. Here, we will discuss the recent advancements regarding the motion manipulation of micro‐ and nanomotors by different approaches.     

Fuel‐Free Synthetic Micro‐/Nanomachines

Inspired by the swimming of natural microorganisms, synthetic micro‐/nanomachines, which convert energy into movement, are able to mimic the function of these amazing natural systems and help humanity by completing environmental and biological tasks. While offering autonomous propulsion, conventional micro‐/nanomachines usually rely on the decomposition of external chemical fuels (e.g., H₂O₂), which greatly hinders their applications in biologically relevant media. Recent developments have resulted in various micro‐/nanomotors that can be powered by biocompatible fuels. Fuel‐free synthetic micro‐/nanomotors, which can move without external chemical fuels, represent another attractive solution for practical applications owing to their biocompatibility and sustainability. Here, recent developments on fuel‐free micro‐/nanomotors (powered by various external stimuli such as light, magnetic, electric, or ultrasonic fields) are summarized, ranging from fabrication to propulsion mechanisms. The applications of these fuel‐free micro‐/nanomotors are also discussed, including nanopatterning, targeted drug/gene delivery, cell manipulation, and precision nanosurgery. With continuous innovation, future autonomous, intelligent and multifunctional fuel‐free micro‐/nanomachines are expected to have a profound impact upon diverse biomedical applications, providing unlimited opportunities beyond one's imagination.     

Thermal Modulation of Nanomotor Movement

Motion control is essential for various applications of man‐made nanomachines. The ability to control and regulate the movement of catalytic nanowire motors is illustrated by applying short heat pulses that allow the motors to be accelerated or slowed down. The accelerated motion observed during the heat pulses is attributed primarily to the thermal activation of the redox reactions of the H₂O₂ fuel at the Pt and Au segments and to the decreased viscosity of the aqueous medium at elevated temperatures. The thermally modulated motion during repetitive temperature on/off cycles is highly reversible and fast, with speeds of 14 and 45 µm s^?1 at 25 and 65 °C, respectively. A wide range of speeds can be generated by tailoring the temperature to yield a linear speed–temperature dependence. Through the use of nickel‐containing nanomotors, the ability to combine the thermally regulated motion of catalytic nanomotors with magnetic guidance is also demonstrated. Such on‐demand control of the movement of nanowire motors holds great promise for complex operations of future manmade nanomachines and for creating more sophisticated nanomotors.     

Recent Progress on Bioinspired Self‐Propelled Micro/Nanomotors via Controlled Molecular Self‐Assembly

The combination of bottom‐up controllable self‐assembly technique with bioinspired design has opened new horizons in the development of self‐propelled synthetic micro/nanomotors. Over the past five years, a significant advances toward the construction of bioinspired self‐propelled micro/nanomotors has been witnessed based on the controlled self‐assembly technique. Such a strategy permits the realization of autonomously synthetic motors with engineering features, such as sizes, shapes, composition, propulsion mechanism, and function. The construction, propulsion mechanism, and movement control of synthetic micro/nanomotors in connection with controlled self‐assembly in recent research activities are summarized. These assembled nanomotors are expected to have a tremendous impact on current artificial nanomachines in future and hold potential promise for biomedical applications including drug targeted delivery, photothermal cancer therapy, biodetoxification, treatment of atherosclerosis, artificial insemination, crushing kidney stones, cleaning wounds, and removing blood clots and parasites.     

Biomimetic Platelet‐Camouflaged Nanorobots for Binding and Isolation of Biological Threats

One emerging and exciting topic in robotics research is the design of micro‐/nanoscale robots for biomedical operations. Unlike industrial robots that are developed primarily to automate routine and dangerous tasks, biomedical nanorobots are designed for complex, physiologically relevant environments, and tasks that involve unanticipated biological events. Here, a biologically interfaced nanorobot is reported, made of magnetic helical nanomotors cloaked with the plasma membrane of human platelets. The resulting biomimetic nanorobots possess a biological membrane coating consisting of diverse functional proteins associated with human platelets. Compared to uncoated nanomotors which experience severe biofouling effects and hence hindered propulsion in whole blood, the platelet‐membrane‐cloaked nanomotors disguise as human platelets and display efficient propulsion in blood over long time periods. The biointerfaced nanorobots display platelet‐mimicking properties, including adhesion and binding to toxins and platelet‐adhering pathogens, such as Shiga toxin and Staphylococcus aureus bacteria. The locomotion capacity and platelet‐mimicking biological function of the biomimetic nanomotors offer efficient binding and isolation of these biological threats. The dynamic biointerfacing platform enabled by platelet‐membrane cloaked nanorobots thus holds considerable promise for diverse biomedical and biodefense applications.     

Printing 1D Assembly Array of Single Particle Resolution for Magnetosensing

Magnetosensing is a ubiquitous ability for many organism species in nature. 1D assembly, especially that arranged in single‐particle‐resolution regulation, is able to sense the direction of magnetic field depending on the enhanced dipolar interaction in the linear orientation. Inspired by the magnetosome structure in magnetotactic bacteria, a 1D assembly array of single particle resolution with controlled length and well‐behaved configuration is prepared via inkjet printing method assisted with magnetic guiding. In the fabrication process, chains in a “tip‐to‐tip” regulation with the desired number of particles are prepared in a confined tiny inkjet‐printed droplet. By adjusting the receding angle of the substrate, the assembled 1D morphology is kept/deteriorated depending on the pinning/depinning behavior during ink evaporation, which leads to the formation of well‐behaved 1D assembly/aggregated dot assembly. Owing to the high‐aspect‐ratio characteristic of the assembled structure, the as‐prepared 1D arrays can be used for magnetic field sensing with anisotropic magnetization M_///M_⊥ up to 6.03.     

Motion Control at the Nanoscale

Synthetic nanoscale motors represent a major step in the development of practical nanomachines. This Review summarizes recent progress towards controlling the movement of fuel‐driven nanomotors and discusses the challenges and opportunities associated with the achievement of such nanoscale motion control. Regulating the movement of artificial nanomotors often follows nature's elegant and remarkable approach for motion control. Such on‐demand control of the movement of artificial nanomotors is essential for performing various tasks and diverse applications. These applications require precise control of the nanomotor direction as well as temporal and spatial regulation of the motor speed. Different approaches for controlling the motion of catalytic nanomotors have been developed recently, including magnetic guidance, thermally driven acceleration, an electrochemical switch, and chemical stimuli (including control of the fuel concentration). Such ability to control the directionality of artificial nanomotors and to regulate their speed offers considerable promise for designing powerful nanomachines capable of operating independently and meeting a wide variety of future technological needs.     

Unlocking the Potential of Magnetotactic Bacteria as Magnetic Hyperthermia Agents

Magnetotactic bacteria are aquatic microorganisms that internally biomineralize chains of magnetic nanoparticles (called magnetosomes) and use them as a compass. Here it is shown that magnetotactic bacteria of the strain Magnetospirillum gryphiswaldense present high potential as magnetic hyperthermia agents for cancer treatment. Their heating efficiency or specific absorption rate is determined using both calorimetric and AC magnetometry methods at different magnetic field amplitudes and frequencies. In addition, the effect of the alignment of the bacteria in the direction of the field during the hyperthermia experiments is also investigated. The experimental results demonstrate that the biological structure of the magnetosome chain of magnetotactic bacteria is perfect to enhance the hyperthermia efficiency. Furthermore, fluorescence and electron microscopy images show that these bacteria can be internalized by human lung carcinoma cells A549, and cytotoxicity studies reveal that they do not affect the viability or growth of the cancer cells. A preliminary in vitro hyperthermia study, working on clinical conditions, reveals that cancer cell proliferation is strongly affected by the hyperthermia treatment, making these bacteria promising candidates for biomedical applications.     

From Strong Dichroic Nanomotor to Polarotactic Microswimmer

Light‐driven micro/nanomotors are promising candidates for long‐envisioned next‐generation nanorobotics for targeted drug delivery, noninvasive surgery, nanofabrication, and beyond. To achieve these fantastic applications, effective control of the micro/nanomotor is essential. Light has been proved as the most versatile method for microswimmer manipulation, while the light propagation direction, intensity, and wavelength have been explored as controlling signals for light‐responsive nanomotors. Here, the controlling method is expanded to the polarization state of the light, and a nanomotor with a significant dichroic ratio is demonstrated. Due to the anisotropic crystal structure, light polarized parallel to the Sb₂Se₃ nanowires is preferentially absorbed. The core–shell Sb₂Se₃/ZnO nanomotor exhibits strong dichroic swimming behavior: the swimming speed is ≈3 times faster when illuminated with parallel polarized light than perpendicular polarized light. Furthermore, by incorporating two cross‐aligned dichroic nanomotors, a polarotactic artificial microswimmer is achieved, which can be navigated by controlling the polarization direction of the incident light. Compared to the well‐studied light‐driven rotary motors based on optical tweezers, this dichroic microswimmer offers eight orders of magnitude light‐intensity reduction, which may enable large‐scale nanomanipulation as well as other heat‐sensitive applications.     

Microbial synthesis of iron-based nanomaterials—A review

Nanoparticles are the materials having dimensions of the order of 100 nm or less. They exhibit a high surface/volume ratio leading to different properties far different from those of the bulk materials. The development of uniform nanoparticles has been intensively pursued because of their technological and fundamental scientific importance. A number of chemical methods are available and are extensively used, but these are often energy intensive and employ toxic chemicals. An alternative approach for the synthesis of uniform nanoparticles is the biological route that occurs at ambient temperature, pressure and at neutral pH. The main aim of this review is to enlist and compare various methods of synthesis of iron-based nanoparticles with emphasis on the biological method. Biologically induced and controlled mineralization mechanisms are the two modes through which the micro-organisms synthesize iron oxide nanoparticles. In biologically induced mineralization (BIM) mode, the environmental factors like pH, pO₂, pCO₂, redox potential, temperature etc govern the synthesis of iron oxide nanoparticles. In contrast, biologically controlled mineralization (BCM) process initiates the micro-organism itself to control the synthesis. BIM can be observed in the Fe(III) reducing bacterial species of Shewanella, Geobacter, Thermoanaerobacter, and sulphate reducing bacterial species of Archaeoglobus fulgidus, Desulfuromonas acetoxidans, whereas BCM mode can be observed in the magnetotactic bacteria (MTB) like Magnetospirillum magnetotacticum, M. gryphiswaldense and sulphate-reducing magnetic bacteria (Desulfovibrio magneticus). Magnetite crystals formed by Fe(III)-reducing bacteria are epicellular, poorly crystalline, irregular in shapes, having a size range of 10–50 nm super-paramagnetic particles, with a saturation magnetization value ranging from 75–77 emu/g and are not aligned in chains. Magnetite crystals produced by MTB have uniform species-specific morphologies and sizes, which are mostly unknown from inorganic systems. The unusual characteristics of magnetosome particles have attracted a great interdisciplinary interest and inspired numerous ideas for their biotechnological applications. The nanoparticles synthesized through biological method are uniform with size ranging from 5 to 100 nm, which can potentially be used for various applications.     

A Versatile Toolkit for Controllable and Highly Selective Multifunctionalization of Bacterial Magnetic Nanoparticles

Their unique material characteristics, i.e. high crystallinity, strong magnetization, uniform shape and size, and the ability to engineer the enveloping membrane in vivo make bacterial magnetosomes highly interesting for many biomedical and biotechnological applications. In this study, a versatile toolkit is developed for the multifunctionalization of magnetic nanoparticles in the magnetotactic bacterium Magnetospirillum gryphiswaldense, and the use of several abundant magnetosome membrane proteins as anchors for functional moieties is explored. High‐level magnetosome display of cargo proteins enables the generation of engineered nanoparticles with several genetically encoded functionalities, including a core–shell structure, magnetization, two different catalytic activities, fluorescence and the presence of a versatile connector that allows the incorporation into a hydrogel‐based matrix by specific coupling reactions. The resulting reusable magnetic composite demonstrates the high potential of synthetic biology for the production of multifunctional nanomaterials, turning the magnetosome surface into a platform for specific versatile display of functional moieties.     

Self‐Propelled Micro/Nanomotors for Sensing and Environmental Remediation

Self‐propelled micro/nanomotors have gained attention for successful application in cargo delivery, therapeutic treatments, sensing, and environmental remediation. Unique characteristics such as high speed, motion control, selectivity, and functionability promote the application of micro/nanomotors in analytical sciences. Here, the recent advancements and main challenges regarding the application of self‐propelled micro/nanomotors in sensing and environmental remediation are discussed. The current state of micro/nanomotors is reviewed, emphasizing the period of the last five years, then their developments into the future applications for enhanced sensing and efficient purification of water resources are extrapolated.     

Bioinspired Soft Microrobots with Precise Magneto-Collective Control for Microvascular Thrombolysis

New-era soft microrobots for biomedical applications need to mimic the essential structures and collective functions of creatures from nature. Biocompatible interfaces, intelligent functionalities, and precise locomotion control in a collective manner are the key parameters to design soft microrobots for the complex bio-environment. In this work, a biomimetic magnetic microrobot (BMM) inspired by magnetotactic bacteria (MTB) with speedy motion response and accurate positioning is developed for targeted thrombolysis. Similar to the magnetosome structure in MTB, the BMM is composed of aligned iron oxide nanoparticle (MNP) chains embedded in a non-swelling microgel shell. Linear chains in BMMs are achieved due to the interparticle dipolar interactions of MNPs under a static magnetic field. Simulation results show that, the degree and speed of assembly is proportional to the field strength. The BMM achieves the maximum speed of 161.7 µm s⁻¹ and accurate positioning control under a rotating magnetic field with less than 4% deviation. Importantly, the locomotion analyses of BMMs demonstrate the frequency-dependent synchronization under 8 Hz and asynchronization at higher frequencies due to the increased drag torque. The BMMs can deliver and release thrombolytic drugs via magneto-collective control, which is promising for ultra-minimal invasive thrombolysis.     

Biocompatible Magnetic Micro- and Nanodevices: Fabrication of FePt Nanopropellers and Cell Transfection

The application of nanoparticles for drug or gene delivery promises benefits in the form of single-cell-specific therapeutic and diagnostic capabilities. Many methods of cell transfection rely on unspecific means to increase the transport of genetic material into cells. Targeted transport is in principle possible with magnetically propelled micromotors, which allow responsive nanoscale actuation and delivery. However, many commonly used magnetic materials (e.g., Ni and Co) are not biocompatible, possess weak magnetic remanence (Fe₃O₄), or cannot be implemented in nanofabrication schemes (NdFeB). Here, it is demonstrated that co-depositing iron (Fe) and platinum (Pt) followed by one single annealing step, without the need for solution processing, yields ferromagnetic FePt nanomotors that are noncytotoxic, biocompatible, and possess a remanence and magnetization that rival those of permanent NdFeB micromagnets. Active cell targeting and magnetic transfection of lung carcinoma cells are demonstrated using gradient-free rotating millitesla fields to drive the FePt nanopropellers. The carcinoma cells express enhanced green fluorescent protein after internalization and cell viability is unaffected by the presence of the FePt nanopropellers. The results establish FePt, prepared in the L1₀ phase, as a promising magnetic material for biomedical applications with superior magnetic performance, especially for micro- and nanodevices.     

Light‐Driven ZnO Brush‐Shaped Self‐Propelled Micromachines for Nitroaromatic Explosives Decomposition

Self‐propelled micromachines have recently attracted lots of attention for environmental remediation. Developing a large‐scale but template‐free fabrication of self‐propelled rod/tubular micro/nanomotors is very crucial but still challenging. Here, a new strategy based on vertically aligned ZnO arrays is employed for the large‐scale and template‐free fabrication of self‐propelled ZnO‐based micromotors with H₂O₂‐free light‐driven propulsion ability. Brush‐shaped ZnO‐based micromotors with different diameters and lengths are fully studied, which present a fast response to multicycles UV light on/off switches with different interval times (2/5 s) in pure water and slow directional motion in aqueous hydrogen peroxide solution in the absence of UV light. Light‐induced electrophoretic and self‐diffusiophoretic effects are responsible for these two different self‐motion behaviors under different conditions, respectively. In addition, the pH of the media and the presence of H₂O₂ show important effects on the motion behavior and microstructure of the ZnO‐based micromotors. Finally, these novel ZnO‐based brush‐shaped micromotors are demonstrated in a proof‐of‐concept study on nitroaromatic explosive degradation, i.e., picric acid. This work opens a completely new avenue for the template‐free fabrication of brush‐shaped light‐responsive micromotors on a large scale based on vertically aligned ZnO arrays.     

Magnetic orientation and magnetic anisotropy in paramagnetic layered oxides containing rare-earth ions

The magnetic anisotropies and easy axes of magnetization at room temperature were determined, and the effects of rare-earth (RE) ions were clarified for RE-based cuprates, RE-doped bismuth-based cuprates and RE-doped Bi-based cobaltite regarding the grain orientation by magnetic field. The easy axis, determined from the powder orientation in a static field of 10 T, depended qualitatively on the type of RE ion for all three systems. On the other hand, the magnetization measurement of the c-axis oriented powders, aligned in static or rotating fields, revealed that the type of RE ion strongly affected not only the directions of the easy axis but also the absolute value of magnetic anisotropy, and an appropriate choice of RE ion is required to minimize the magnetic field used for grain orientation. We also studied the possibility of triaxial grain orientation in high-critical-temperature superconductors by a modulated oval magnetic field. In particular, triaxial orientation was attempted in a high-oxygen-pressure phase of orthorhombic RE-based cuprates Y₂Ba₄Cu₇O_y. Although the experiment was performed in epoxy resin, which is not practical, in-plane alignment within 3° was achieved.     

非晶丝微磁化线圈磁电阻抗效应研究

本文研究了铁基及钴基非晶态合金丝在由微磁经线圈所产生的轴向交变磁场的作用下所呈现的磁电阻抗效应，经出了一些测试结果，结果表明，微磁化线圈两端的电压信号峰－峰值随轴向外磁场Ｈｅ的增加而单调减少，钴基非晶丝可呈现巨磁电阻抗效应，利用该效应可制成新型磁敏元件及器件。     

Characterization of magnetotactic bacteria and their magnetosomes isolated from Tieshan iron ore in Hubei Province of China

Several magnetotactic bacteria (MTB) have been isolated from iron cap belt, surface soil of intermediate belt and “primary iron ore belt” of Tieshan iron ore in Hubei Province, China. These magnetotactic bacteria were cultivated in enrichment medium at room temperature (25–30 °C), with oxygen concentration of 5–10% under the field of a permanent magnet. The magnetotactic bacteria were cocci or rods. They contained two or more magnetosomes under transmission electron microscope (TEM H-7000 FA), and the magnetosomes were in the shapes of rounded, triangular, rectangular and irregular. Energy spectrum analysis with Jeol 2000 transmission electron microscope (JEM2000FXII) equipped with energy dispersive system (EDS) controlled by Oxford Instruments Analytical system (INCA) showed that iron oxides were the main component of the magnetic particles.     

Self‐Organized Multiconstituent Catalytic Nanomotors

Self‐organized catalytic nanomotors consisting of more than one individual component are presented. Tadpole‐like catalytic nanomotors fabricated by dynamic shadowing growth (DSG) self‐organize randomly to form two‐nanomotor clusters (≈1–3% yield) that spin as opposed to circular motion exhibited by the individual structures. By introducing magnetic materials to another system, self‐assembled “helicopter” nanomotors consisting of a V‐shaped nanomotor and a microbead are formed with ≈25% yield, showing a significantly higher yield than the control (0%). A flexible swimmer system that performs complex swimming, such as maneuvering around stationary objects, is also presented. These nanomotor systems are inherently more complex than those previously studied and may be the next step towards building sophisticated multifunctional nanomachinery systems.