Antibacterial And Biofilm Removal Strategies Based On Micro/nanomotors In The Biomedical Field.

Bacterial infection, which can trigger varieties of diseases and tens of thousands of deaths each year, poses  serious threats to human health. Particularly, the new dilemma caused by biofilms is gradually becoming a severe and tough problem in the biomedical field. Thus, the strategies to address these problems are considered an urgent task at present. Micro/nanomotors (MNMs), also named micro/nanoscale robots, are mostly driven by chemical energy or external field, exhibiting strong diffusion and self-propulsion in the liquid media, which has the potential for antibacterial applications. In particular, when MNMs are assembled in swarms, they become robust and efficient for biofilm removal. However, there is a lack of comprehensive review discussing the progress in this aspect. Bearing it in mind and based on our own research experience in this regard, the studies on MNMs driven by different mechanisms orchestrated for antibacterial activity and biofilm removal are timely and concisely summarized and discussed in this work, aiming to show the advantages of MNMs brought to this field. In addition, an outlook was proposed, hoping to provide the fundamental guidance for future development in this area.

Polysaccharide-Based Micro/Nanomotors for Active Ingredient Delivery in Food.

Micro/nanomotors (MNMs) are miniature devices that can generate energy through chemical reactions or physical processes, utilizing this energy for movement. By virtue of their small size, self-propulsion, precise positioning within a small range, and ability to access microenvironments, MNMs have been applied in various fields including sensing, biomedical applications, and pollutant adsorption. However, the development of food-grade MNMs and their application in food delivery systems have been scarcely reported. Currently, there are various issues with the decomposition, oxidation, or inability to maintain the activity of some nutrients or bioactive substances, such as the limited application of curcumin (Cur) in food. Compared to traditional delivery systems, MNMs can adjust the transport speed and direction as needed, effectively protecting bioactive substances during delivery and achieving efficient transportation. Therefore, this study utilizes polysaccharides as the substrate, employing a simple, rapid, and pollution-free template method to prepare polysaccharide-based microtubes (PMTs) and polysaccharide-based micro/nanomotors (PMNMs). PMNMs can achieve multifunctional propulsion by modifying ferrosoferric oxide (Fe3O4), platinum (Pt), and glucose oxidase (GOx). Fe-PMNMs and Pt-PMNMs exhibit excellent photothermal conversion performance, showing promise for applications in photothermal therapy. Moreover, PMNMs can effectively deliver curcumin, achieving the effective delivery of nutrients and exerting the anti-inflammatory performance of the system.

Ion-Exchange Enabled Dual-Functional Swarms with Reconfigurability and Magnetic Controllability.

In nature, many organisms are capable of self-organizing into collective groups through local communications to perform complex tasks that individuals cannot complete. To date, the reported artificial microswarms either rely on toxic chemical reactions for communication or lack the hierarchical controllability and functionality, which is unfavorable for practical applications. To this end, this exploits the ion-exchange reaction enabled hierarchical swarm composed of cationic ion exchange resin and magnetic microspheres of internal information exchange. The swarm is reconfigurable under magnetic fields, generating ordered structures of controllable mobilities and even reversed hierarchy, able to navigate in confined and complex environments. Moreover, the swarm shows interesting communications among each other, such as merging, splitting, and member exchange, forming multi-leader groups, living crystals, and complex vortices. Furthermore, the swarm functions as a dual-functional microreactor, which can load, transport, and release drugs in a pH-enhanced manner, as well as effectively degrade antibiotics via light-enhanced Fenton-like reaction in polluted water. The organized structure of the swarm greatly improves the drug loading/transport efficiency and the local concentration of catalysts for fast pollutant removal. This design lays the foundation for the design of dual-functional micro/nanorobots for intelligent drug delivery and advanced environmental remediation.

Weak Ion-Exchange Based Magnetic Swarm for Targeted Drug Delivery and Chemotherapy.

Swimming microrobots that are actuated by multiple stimuli/fields display various intriguing collective behaviors, ranging from phase separation to clustering and giant number fluctuation; however, it is still chanllenging to achieve multiple responses and functionalities within one colloidal system to emulate high environmental adaptability and improved tasking capability of natural swarms. In this work, a weak ion-exchange based swarm is presented that can self-organize and reconfigure by chemical, light, and magnetic fields, showing living crystal, amorphous glass, liquid, chain, and wheel-like structures. By changing the frequency and strength of the rotating magnetic field, various well-controlled and fast transformations are obtained. Experiments show the high adaptability and functionality of the microrobot swarm in delivering drugs in confined spaces, such as narrow channels with turns or obstacles. The drug-carrying swarm exhibits excellent chemtherapy for Hela and CT26 cells due to the pH-enhanced drug release and locomotion. This reconfigurable microswarm provides a new platform for biomedical and environmental applications.

Focus on the performance enhancement of micro/nanomotor-based biosensors.

Micro/nanomotors (MNMs) emerge as a vital candidate for biosensing due to its nano-size structure, high surface-to-area ratio, directional mobility, biocompatibility, and ease of functionalization, therefore being able to detect objects with high efficiency, precision, and selectivity. The driving mode, nanostructure, materials property, preparation technique, and biosensing applications have been thoroughly discussed in publications. To promote the MNMs-based biosensors from in vitro to in vivo, it is necessary to give a comprehensive discussion from the perspective of sensing performances enhancement. However, until now, there is few reviews dedicated to the systematic discussion on the multiple performance enhancement schemes and the current challenges of MNMs-based biosensors. Bearing it in mind and based on our research experience in this field, we summarized the enhancement methods for biosensing properties such as sensitivity, selectivity, detection time, biocompatibility, simplify system operation, and environmental availability. We hope that this review provides the readers with fundamental understanding on performance enhancement schemes for MNMs-based biosensors.

Construction of intelligent moving micro/nanomotors and their applications in biosensing and disease treatment.

Micro/nanomotors are containers that pass through liquid media and carry cargo. Because they are tiny, micro/nanomotors exhibit excellent potential for biosensing and disease treatment applications. However, their size also makes overcoming random Brownian forces very challenging for micro/nanomotors moving on targets. Additionally, to achieve desired practical applications, the expensive materials, short lifetimes, poor biocompatibility, complex preparation methods, and side effects of micro/nanomotors must be addressed, and potential adverse effects must be evaluated both in vivo and in practical applications. This has led to the continuous development of key materials for driving micro/nanomotors. In this work, we review the working principles of micro/nanomotors. Metallic and nonmetallic nanocomplexes, enzymes, and living cells are explored as key materials for driving micro/nanomotors. We also consider the effects of exogenous stimulations and endogenous substance conditions on micro/nanomotor motions. The discussion focuses on micro/nanomotor applications in biosensing, treating cancer and gynecological diseases, and assisted fertilization. By addressing micro/nanomotor shortcomings, we propose directions for further developing and applying micro/nanomotors.

Micro/nanomotor technology: the new era for food safety control.

Food poisoning caused by eating contaminated food remains a threat to global public health. Making the situation even worse is the aggravated global environmental pollution, which poses a major threat to the safety of agricultural resources. Food adulteration has been rampant owing to negligent national food safety regulations. The speed at which contaminated food is detected and disposed of determines the extent to which consumers' lives are safeguarded and agricultural economic losses are prevented. Micro/nanomotors offer a high-speed mobile loading platform that substantially increases the chemical reaction rates and, accordingly, exhibit great potential as alternatives to conventional detection and degradation techniques. This review summarizes the propulsion modes applicable to micro/nanomotors in food systems and the advantages of using micro/nanomotors, highlighting examples of their potential use in recent years for the detection and removal of food contaminants. Micro/nanomotors are an emerging technology for food applications that is moving toward mass production, simple preparation, and important functions.

Dual-Mode-Driven Micromotor Based on Foam-like Carbon Nitride and Fe3O4 with Improved Manipulation and Photocatalytic Performance.

Micro/nanomotors have emerged as a vibrant research topic in biomedical and environmental fields due to their attractive self-propulsion as well as small-scale functionalities. However, single actuated micro/nanomotors are not adaptive in facing intricate natural and industrial environments. Herein, we propose a new dual-mode-driven micromotor based on foam-like carbon nitride (f-C3N4) with precipitated Fe3O4 nanoparticles, namely, Fe3O4/f-C3N4, powered by chemical/magnetic stimuli for rapid reduction of organic pollutants. The Fe3O4/f-C3N4 motor composed of a three-dimensional (3D) porous "foam-like" structure and precipitated Fe3O4 nanoparticles (ca. 50 nm) not only exhibits efficient photocatalytic performance under visible light but also shows versatile and programmable motion behavior under the control of external magnetic fields. The aggregation of the micromotor under an external rotating magnetic field further enhances the catalytic activity by the increased local catalyst concentration. Furthermore, the magnetic property endows the micromotor with easy recyclability. This study provides a novel dual-mode-driven micromotor for antibiotics removal with magnetic field and light-enhanced performance in industrial wastewater treatment at a low cost.

Generic Rules for Distinguishing Autophoretic Colloidal Motors.

Distinguishing the operating mechanisms of nano- and micromotors powered by chemical gradients, i.e. "autophoresis", holds the key for fundamental and applied reasons. In this article, we propose and experimentally confirm that the speeds of a self-diffusiophoretic colloidal motor scale inversely to its population density but not for self-electrophoretic motors, because the former is an ion source and thus increases the solution ionic strength over time while the latter does not. They also form clusters in visually distinguishable and quantifiable ways. This pair of rules is simple, powerful, and insensitive to the specific material composition, shape or size of a colloidal motor, and does not require any measurement beyond typical microscopy. These rules are not only useful in clarifying the operating mechanisms of typical autophoretic micromotors, but also in predicting the dynamics of unconventional ones that are yet to be experimentally realized, even those involving enzymes.

Oxygen Generation Using Catalytic Nano/Micromotors.

Gaseous oxygen plays a vital role in driving the metabolism of living organisms and has multiple agricultural, medical, and technological applications. Different methods have been discovered to produce oxygen, including plants, oxygen concentrators and catalytic reactions. However, many such approaches are relatively expensive, involve challenges, complexities in post-production processes or generate undesired reaction products. Catalytic oxygen generation using hydrogen peroxide is one of the simplest and cleanest methods to produce oxygen in the required quantities. Chemically powered micro/nanomotors, capable of self-propulsion in liquid media, offer convenient and economic platforms for on-the-fly generation of gaseous oxygen on demand. Micromotors have opened up opportunities for controlled oxygen generation and transport under complex conditions, critical medical diagnostics and therapy. Mobile oxygen micro-carriers help better understand the energy transduction efficiencies of micro/nanoscopic active matter by careful selection of catalytic materials, fuel compositions and concentrations, catalyst surface curvatures and catalytic particle size, which opens avenues for controllable oxygen release on the level of a single catalytic microreactor. This review discusses various micro/nanomotor systems capable of functioning as mobile oxygen generators while highlighting their features, efficiencies and application potentials in different fields.

Current status of micro/nanomotors in drug delivery.

Synthetic micro/nanomotors (MNMs) are novel, self-propelled nano or microscale devices that are widely used in drug transport, cell stimulation and isolation, bio-imaging, diagnostic and monitoring, sensing, photocatalysis and environmental remediation. Various preparation methods and propulsion mechanisms make MNMs "tailormade" nanosystems for the intended purpose or use. As the one of the newest members of nano carriers, MNMs open a new perspective especially for rapid drug transport and gene delivery. Although there exists limited number of in-vivo studies for drug delivery purposes, existence of in-vitro supportive data strongly encourages researchers to move on in this field and benefit from the manoeuvre capability of these novel systems. In this article, we reviewed the preparation and propulsion mechanisms of nanomotors in various fields with special attention to drug delivery systems.

Fantastic Voyage of Nanomotors into the Cell.

Richard Feynman's 1959 vision of controlling devices at small scales and swallowing the surgeon has inspired the science-fiction Fantastic Voyage film and has played a crucial role in the rapid development of the microrobotics field. Sixty years later, we are currently witnessing a dramatic progress in this field, with artificial micro- and nanoscale robots moving within confined spaces, down to the cellular level, and performing a wide range of biomedical applications within the cellular interior while addressing the limitations of common passive nanosystems. In this review article, we discuss key recent advances in the field of micro/nanomotors toward important cellular applications. Specifically, we outline the distinct capabilities of nanoscale motors for such cellular applications and illustrate how the active movement of nanomotors leads to distinct advantages of rapid cell penetration, accelerated intracellular sensing, and effective intracellular delivery toward enhanced therapeutic efficiencies. We finalize by discussing the future prospects and key challenges that such micromotor technology face toward implementing practical intracellular applications. By increasing our knowledge of nanomotors' cell entry and of their behavior within the intracellular space, and by successfully addressing key challenges, we expect that next-generation nanomotors will lead to exciting advances toward cell-based diagnostics and therapy.

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.

Study on Tumor Drugs for Targeted Therapy Based on Micro-nanomotor / 中国药师

Objective:To investigate the targeted motion and controllable release of tumor drugs based on micromotor. Methods:The directional movement of Janus micro-capsules was achieved through an external magnetic field,and the controllable release of tumor drugs was induced by near-infrared laser.Results:During the same period, the movement speed of the Janus capsules micromotor was the fastest(36.8 μm·s-1,approximately equalled to 3 body length·s-1) in 15% H2O2solution. Under the control of the external magnetic field, the Janus capsules micromotor could move along the scheduled trajectory close to the area of HeLa cells. Through the irradiation of near-infrared laser, the Janus capsules micromotor was broken and released the loaded drugs quickly. Conclusion:The Janus capsule micromotor studied in the paper can be used for targeted drug delivery safely and effectively,therefore,it shows good application prospect in the field of tumor diagnosis and treatment.

Rheotaxis of Bimetallic Micromotors Driven by Chemical-Acoustic Hybrid Power.

Rheotaxis is a common phenomenon in nature that refers to the directed movement of micro-organisms as a result of shear flow. The ability to mimic natural rheotaxis using synthetic micro/nanomotors adds functionality to enable their applications in biomedicine and chemistry. Here, we present a hybrid strategy that can achieve both positive and negative rheotaxis of synthetic bimetallic micromotors by employing a combination of chemical fuel and acoustic force. An acoustofluidic device is developed for the integration of the two propulsion mechanisms. Using acoustic force alone, bimetallic microrods are propelled along the bottom surface in the center of a fluid channel. The leading end of the microrod is always the less dense end, as established in earlier experiments. With chemical fuel (H2O2) alone, the microrods orient themselves with their anode end against the flow when shear flow is present. Numerical simulations confirm that this orientation results from tilting of the microrods relative to the bottom surface of the channel, which is caused by catalytically driven electro-osmotic flow. By combining this catalytic orientation effect with more powerful, density-dependent acoustic propulsion, both positive and negative rheotaxis can be achieved. The ability to respond to flow stimuli and collectively propel synthetic microswimmers in a directed manner indicates an important step toward practical applications.

Self-Propelled Metal-Polymer Hybrid Micromachines with Bending and Rotational Motions.

Two self-propelled micromachines were fabricated with gold/platinum micromotors that exhibit simple translational motion in a fuel solution. In each one, two micromotors were connected with a joint of polymer tube formed by stacking cationic poly(allylamine hydrochloride) (PAH) and anionic poly(acrylic acid) (PAA) using a layer-by-layer technique. A bent structure was created by making one longitudinal side of the joint more swellable with alkaline treatment. The joint containing fewer PAA/PAH bilayers was flexible and allowed a larger range of Brownian angular fluctuation. In the fuel solution, bending and stable rotation were observed for the micromotors tethered with soft and rigid angled joints, respectively. The radius and angular velocity of the rotation depended on the angle of the joint. Such tethered micromotors can be used to realize sophisticated micro/nanomachines for microscale surgery and drug delivery.