Magnesium‐Based Micromotors: Water‐Powered Propulsion,Multifunctionality, and Biomedical and Environmental Applications

The new capabilities and functionalities of synthetic micro/nanomotors open up considerable opportunities for diverse environmental and biomedical applications. Water‐powered micromachines are particularly attractive for realizing many of these applications. Magnesium‐based motors directly use water as fuel to generate hydrogen bubbles for their propulsion, eliminating the requirement of common toxic fuels. This Review highlights the development of new Mg‐based micromotors and discusses the chemistry that makes it extremely attractive for micromotor applications. Understanding these Mg properties and its transient nature is essential for controlling the propulsion efficiency, lifetime, and overall performance. The unique and attractive behavior of Mg offers significant advantages, including efficient water‐powered movement, remarkable biocompatibility, controlled degradation, convenient functionalization, and built‐in acid neutralization ability, and has paved the way for multifunctional micromachines for diverse real‐life applications, including operation in living animals. A wide range of such Mg motor‐based applications, including the detection and destruction of environmental threats, effective in‐vivo cargo delivery, and autonomous release, have been demonstrated. In conclusion, the current challenges, future opportunities, and performance improvements of the Mg‐based micromotors are discussed. With continuous innovation and attention to key challenges, it is expected that Mg‐based motors will have a profound impact on diverse biomedical and environmental applications.     

Multicompartment Tubular Micromotors Toward Enhanced Localized Active Delivery

A tubular micromotor with spatially resolved compartments is presented toward efficient site-specific cargo delivery, with a back-end zinc (Zn) propellant engine segment and an upfront cargo-loaded gelatin segment further protected by a pH-responsive cap. The multicompartment micromotors display strong gastric-powered propulsion with tunable lifetime depending on the Zn segment length. Such propulsion significantly enhances the motor distribution and retention in the gastric tissues, by pushing and impinging the front-end cargo segment onto the stomach wall. Once the micromotor penetrates the gastric mucosa (pH ≥ 6.0), its pH-responsive cap dissolves, promoting the autonomous localized cargo release. The fabrication process, physicochemical properties, and propulsion behavior are systematically tested and discussed. Using a mouse model, the multicompartment motors, loaded with a model cargo, demonstrate a homogeneous cargo distribution along with approximately four-fold enhanced retention in the gastric lining compared to monocompartment motors, while showing no apparent toxicity. Therapeutic payloads can also be loaded into the pH-responsive cap, in addition to the gelatin-based compartment, leading to concurrent delivery and sequential release of dual cargos toward combinatorial therapy. Overall, this multicompartment micromotor system provides unique features and advantages that will further advance the development of synthetic micromotors for active transport and localized delivery of biomedical cargos.     

Design,Properties, and In Vivo Behavior of Super­paramagnetic Persistent Luminescence Nanohybrids

With the fast development of noninvasive diagnosis, the design of multimodal imaging probes has become a promising challenge. If many monofunctional nanocarriers have already proven their efficiency, only few multifunctional nanoprobes have been able to combine the advantages of diverse imaging modalities. An innovative nanoprobe called mesoporous persistent luminescence magnetic nanohybrids (MPNHs) is described that shows both optical and magnetic resonance imaging (MRI) properties intended for in vivo multimodal imaging in small animals. MPNHs are based on the assembly of chromium‐doped zinc gallate oxide and ultrasmall superparamagnetic iron oxide nanoparticles embedded in a mesoporous silica shell. MPNHs combine the optical advantages of persistent luminescence, such as real time imaging with highly sensitive and photostable detection, and MRI negative contrast properties that ensure in vivo imaging with rather high spatial resolution. In addition to their imaging capabilities, these MPNHs can be motioned in vitro with a magnet, which opens multiple perspectives in magnetic vectorization and cell therapy research.     

Programmable Construction of Peptide‐Based Materials in Living Subjects: From Modular Design and Morphological Control to Theranostics

Self‐assembled nanomaterials show potential high efficiency as theranostics for high‐performance bioimaging and disease treatment. However, the superstructures of pre‐assembled nanomaterials may change in the complicated physiological conditions, resulting in compromised properties and/or biofunctions. Taking advantage of chemical self‐assembly and biomedicine, a new strategy of “in vivo self‐assembly” is proposed to in situ construct functional nanomaterials in living subjects to explore new biological effects. Herein, recent advances on peptide‐based nanomaterials constructed by the in vivo self‐assembly strategy are summarized. Modular peptide building blocks with various functions, such as targeting, self‐assembly, tailoring, and biofunctional motifs, are employed for the construction of nanomaterials. Then, self‐assembly of these building blocks in living systems to construct various morphologies of nanostructures and corresponding unique biological effects, such as assembly/aggregation‐induced retention (AIR), are introduced, followed by their applications in high‐performance drug delivery and bioimaging. Finally, an outlook and perspective toward future developments of in vivo self‐assembled peptide‐based nanomaterials for translational medicine are concluded.     

Self‐Assembly of Graphene Oxide at Interfaces

Due to its amphiphilic property, graphene oxide (GO) can achieve a variety of nanostructures with different morphologies (for example membranes, hydrogel, crumpled particles, hollow spheres, sack‐cargo particles, Pickering emulsions, and so on) by self‐assembly. The self‐assembly is mostly derived from the self‐concentration of GO sheets at various interfaces, including liquid‐air, liquid‐liquid and liquid‐solid interfaces. This paper gives a comprehensive review of these assembly phenomena of GO at the three types of interfaces, the derived interfacial self‐assembly techniques, and the as‐obtained assembled materials and their properties. The interfacial self‐assembly of GO, enabled by its fantastic features including the amphiphilicity, the negatively charged nature, abundant oxygen‐containing groups and two‐dimensional flexibility, is highlighted as an easy and well‐controlled strategy for the design and preparation of functionalized carbon materials, and the use of self‐assembly for uniform hybridization is addressed for preparing hybrid carbon materials with various functions. A number of new exciting and potential applications are also presented for the assembled GO‐based materials. This contribution concludes with some personal perspectives on future challenges before interfacial self‐assembly may become a major strategy for the application‐targeted design and preparation of functionalized carbon materials.     

Template Electrosynthesis of High‐Performance Graphene Microengines

Template‐prepared graphene/Pt and graphene/Au tubular microengines, with extremely high electrocatalytic activity and propulsion efficiency, are described. The new bubble‐propelled graphene/metal micromotors are synthesized rapidly and inexpensively by the direct electrodeposition of graphene oxide (GO) within the conical pores of a polycarbonate template membrane followed by deposition of the inner metal layer. The presence of high number of edges and defects in the graphene layer results in highly reactive microporous Pt or Au catalytic structures. The high catalytic activity leads to an ultrafast bubble propulsion (as high as 170 body lengths/sec) and operation at extremely low levels (0.1%) of the peroxide fuel. The effect of such dramatically enhanced catalytic surface area on the bubble growth and motor speed has been theoretically modeled. The template‐prepared graphene‐based microengines display distinct moving trajectories, along with long microbubble tails. The fast catalytic locomotion and attractive performance of the new graphene/Pt micromotors hold considerable promise for diverse applications.     

Functionalized micromachines for selective and rapid isolation of nucleic acid targets from complex samples

The transport properties of single-strand DNA probe-modified self-propelling micromachines are exploited for "on-the-fly" hybridization and selective single-step isolation of target nucleic acids from "raw" microliter biological samples (serum, urine, crude E. coli lysate, saliva). The rapid movement of the guided modified microrockets induces fluid convection, which enhances the hybridization efficiency, thus enabling the rapid and selective isolation of nucleic acid targets from untreated samples. The integration of these autonomous microrockets into a lab-on-chip device that provides both nucleic acid isolation and downstream analysis could thus be attractive for diverse applications.     

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.     

MOFBOTS: Metal–Organic‐Framework‐Based Biomedical Microrobots

Motile metal?organic frameworks (MOFs) are potential candidates to serve as small‐scale robotic platforms for applications in environmental remediation, targeted drug delivery, or nanosurgery. Here, magnetic helical microstructures coated with a kind of zinc‐based MOF, zeolitic imidazole framework‐8 (ZIF‐8), with biocompatibility characteristics and pH‐responsive features, are successfully fabricated. Moreover, it is shown that this highly integrated multifunctional device can swim along predesigned tracks under the control of weak rotational magnetic fields. The proposed systems can achieve single‐cell targeting in a cell culture media and a controlled delivery of cargo payloads inside a complex microfluidic channel network. This new approach toward the fabrication of integrated multifunctional systems will open new avenues in soft microrobotics beyond current applications.     

Magnetic Nanomaterials for Advanced Regenerative Medicine: The Promise and Challenges

The recent emergence of numerous nanotechnologies is expected to facilitate the development of regenerative medicine, which is a tissue regeneration technique based on the replacement/repair of diseased tissue or organs to restore the function of lost, damaged, and aging cells in the human body. In particular, the unique magnetic properties and specific dimensions of magnetic nanomaterials make them promising innovative components capable of significantly advancing the field of tissue regeneration. Their potential applications in tissue regeneration are the focus here, beginning with the fundamentals of magnetic nanomaterials. How nanomaterials—both those that are intrinsically magnetic and those that respond to an externally applied magnetic field—can enhance the efficiency of tissue regeneration is also described. Applications including magnetically controlled cargo delivery and release, real‐time visualization and tracking of transplanted cells, magnetic regulation of cell proliferation/differentiation, and magnetic activation of targeted ion channels and signal pathways involved in regeneration are highlighted, and comments on the perspectives and challenges in magnetic nanomaterial‐based tissue regeneration are given.     

Self‐Assembly Toolbox of Tailored Supramolecular Architectures Based on an Amphiphilic Protein Library

The molecular structuring of complex architectures and the enclosure of space are essential requirements for technical and living systems. Self‐assembly of supramolecular structures with desired shape, size, and stability remains challenging since it requires precise regulation of physicochemical and conformational properties of the components. Here a general platform for controlled self‐assembly of tailored amphiphilic elastin‐like proteins into desired supramolecular protein assemblies ranging from spherical coacervates over molecularly defined twisted fibers to stable unilamellar vesicles is introduced. The described assembly protocols efficiently yield protein membrane–based compartments (PMBC) with adjustable size, stability, and net surface charge. PMBCs demonstrate membrane fusion and phase separation behavior and are able to encapsulate structurally and chemically diverse cargo molecules ranging from small molecules to naturally folded proteins. The ability to engineer tailored supramolecular architectures with defined fusion behavior, tunable properties, and encapsulated cargo paves the road for novel drug delivery systems, the design of artificial cells, and confined catalytic nanofactories.     

Biohybrid Microtube Swimmers Driven by Single Captured Bacteria

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

Inorganic Nanoparticles for MRI Contrast Agents

Various inorganic nanoparticles have been used as magnetic resonance imaging (MRI) contrast agents due to their unique properties, such as large surface area and efficient contrasting effect. Since the first use of superparamagnetic iron oxide (SPIO) as a liver contrast agent, nanoparticulate MRI contrast agents have attracted a lot of attention. Magnetic iron oxide nanoparticles have been extensively used as MRI contrast agents due to their ability to shorten T2* relaxation times in the liver, spleen, and bone marrow. More recently, uniform ferrite nanoparticles with high crystallinity have been successfully employed as new T2 MRI contrast agents with improved relaxation properties. Iron oxide nanoparticles functionalized with targeting agents have been used for targeted imaging via the site‐specific accumulation of nanoparticles at the targets of interest. Recently, extensive research has been conducted to develop nanoparticle‐based T1 contrast agents to overcome the drawbacks of iron oxide nanoparticle‐based negative T2 contrast agents. In this report, we summarize the recent progress in inorganic nanoparticle‐based MRI contrast agents.     

Stimulus Responsive 3D Assembly for Spatially Resolved Bifunctional Sensors

3D electronic/optoelectronic devices have shown great potentials for various applications due to their unique properties inherited not only from functional materials, but also from 3D architectures. Although a variety of fabrication methods including mechanically guided assembly have been reported, the resulting 3D devices show no stimuli‐responsive functions or are not free standing, thereby limiting their applications. Herein, the stimulus responsive assembly of complex 3D structures driven by temperature‐responsive hydrogels is demonstrated for applications in 3D multifunctional sensors. The assembly driving force, compressive buckling, arises from the volume shrinkage of the responsive hydrogel substrates when they are heated above the lower critical solution temperature. Driven by the compressive buckling force, the 2D‐formed membrane materials, which are pre‐defined and selectively bonded to the substrates, are then assembled to 3D structures. They include “tent,” “tower,” “two‐floor pavilion,” “dome,” “basket,” and “nested‐cages” with delicate geometries. Moreover, the demonstrated 3D bifunctional sensors based on laser induced graphene show capability of spatially resolved tactile sensing and temperature sensing. These multifunctional 3D sensors would open new applications in soft robotics, bioelectronics, micro‐electromechanical systems, and others.     

NiFe films deposited by sputter gun and applications to bubble devices

The sputter gun system has a unique feature which is that the substrate holder is electrically isolated from and physically outside the cathode and anode gun assembly. As a result the substrate surface temperature can be maintained at a lower level than that for the conventional diode sputtering system. This feature is particularly useful for metallization by the lift-off process. NiFe films with excellent physical and magnetic properties have been obtained. The application to overlay patterns for single-level masking bubble devices is presented.     

New Templated Ostwald Ripening Process of Mesostructured FeOOH for Third‐Harmonic Generation Bioimaging

Emerging advances in iron oxide nanoparticles exploit their high magnetization for various applications, such as bioseparation, hyperthermia, and magnetic resonance imaging. In contrast to their excellent magnetic performance, the harmonic generation and luminescence properties of iron oxide nanoparticles have not been thoroughly explored, thus limiting their development as a tool in photomedicine. In this work, a seed/growth‐inspired synthesis is developed combined with primary mineralization and a ligand‐assisted secondary growth strategy to prepare mesostructured α‐FeOOH nanorods (NRs). The sub‐wavelength heterogeneity of the refractive index leads to enhanced third‐harmonic generation (THG) signals under near‐infrared excited wavelengths at 1230 nm. The as‐prepared NRs exhibit an 11‐fold stronger THG intensity compared to bare α‐FeOOH NRs. Using these unique nonlinear optical properties, it is demonstrated that mesostructured α‐FeOOH NRs can serve as biocompatible and nonbleaching contrast agents in THG microscopy for long‐term labeling of cells as well as in angiography in vivo by modifying lectin to enhance the binding efficiency to the glycocalyx layers on the wall of blood vessels. These results provide a new insight into Fe‐based nanoplatforms capable of emitting coherent light as molecular probes in optical microscopy, thus establishing a complementary microscopic imaging method for macroscopic magnetic imaging systems.     

Catalytic nanomotors: fabrication,mechanism, and applications

Catalytic nanomotors are nano-to-micrometer-sized actuators that carry an on-board catalyst and convert local chemical fuel in solution into mechanical work. The location of this catalyst as well as the geometry of the structure dictate the swimming behaviors exhibited. The nanomotors can occur naturally in organic molecules, combine natural and artificial parts to form hybrid nanomotors or be purely artificial. Fabrication techniques consist of template directed electroplating, lithography, physical vapor deposition, and other advanced growth methods. Various physical and chemical propulsion mechanisms have been proposed to explain the motion behaviors including diffusiophoresis, bubble propulsion, interfacial tension gradients, and self-electropho-resis. The control and manipulation based upon external fields, catalytic alloys, and motion control through thermal modulation are discussed as well. Catalytic nanomotors represent an exciting technological challenge with the end goal being practical functional nanomachines that can perform a variety of tasks at the nanoscale.     

A Modular System for the Design of Stimuli‐Responsive Multifunctional Nanoparticle Aggregates by Use of Host–Guest Chemistry

A self‐assembly approach for the design of multifunctional nanomaterials consisting of different nanoparticles (gold, iron oxide, and lanthanide‐doped LiYF₄) is developed. This modular system takes advantage of the light‐responsive supramolecular host–guest chemistry of β‐cyclodextrin and arylazopyrazole, which enables the dynamic and reversible self‐assembly of particles to spherical nanoparticle aggregates in aqueous solution. Due to the magnetic iron oxide nanoparticles, the aggregates can be manipulated by an external magnetic field leading to the formation of linear structures. As a result of the integration of upconversion nanoparticles, the aggregates are additionally responsive to near‐infrared light and can be redispersed by use of the upconversion effect. By varying the nanoparticle and linker concentrations the composition, size, shape, and properties of the multifunctional nanoparticle aggregates can be fine‐tuned.     

Polyphenol‐Inspired Facile Construction of Smart Assemblies for ATP‐ and pH‐Responsive Tumor MR/Optical Imaging and Photothermal Therapy

Smart assemblies have attracted increased interest in various areas, especially in developing novel stimuli‐responsive theranostics. Herein, commercially available, natural tannic acid (TA) and iron oxide nanoparticles (Fe₃O₄ NPs) are utilized as models to construct smart magnetic assemblies based on polyphenol‐inspired NPs–phenolic self‐assembly between NPs and TA. Interestingly, the magnetic assemblies can be specially disassembled by adenosine triphosphate, which shows a stronger affinity to Fe₃O₄ NPs than that of TA and partly replaces the surface coordinated TA. The disassembly can further be facilitated by the acidic environment hence causing the remarkable change of the transverse relaxivity and potent “turn‐on” of fluorescence (FL) signals. Therefore, the assemblies for specific and sensitive tumor magnetic resonance and FL dual‐modal imaging and photothermal therapy after intravenous injection of the assemblies are successfully employed. This work not only provides understandings on the self‐assembly between NPs and polyphenols, but also will open new insights for facilely constructing versatile assemblies and extending their biomedical applications.