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Micro-/nanorobots (MNRs) can be autonomously propelled on demand in complex biological environments and thus may bring revolutionary changes to biomedicines. Fluorescence has been widely used in real-time imaging, chemo-/biosensing, and photo-(chemo-) therapy. The integration of MNRs with fluorescence generates fluorescent MNRs with unique advantages of optical trackability, on-the-fly environmental sensitivity, and targeting chemo-/photon-induced cytotoxicity. This review provides an up-to-date overview of fluorescent MNRs. After the highlighted elucidation about MNRs of various propulsion mechanisms and the introductory information on fluorescence with emphasis on the fluorescent mechanisms and materials, we systematically illustrate the design and preparation strategies to integrate MNRs with fluorescent substances and their biomedical applications in imaging-guided drug delivery, intelligent on-the-fly sensing and photo-(chemo-) therapy. In the end, we summarize the main challenges and provide an outlook on the future directions of fluorescent MNRs. This work is expected to attract and inspire researchers from different communities to advance the creation and practical application of fluorescent MNRs on a broad horizon.
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Sistemas de Liberación de Medicamentos , FluorescenciaRESUMEN
Micro/nanorobots hold the potential to revolutionize biomedicine by executing diverse tasks in hard-to-reach biological environments. Nevertheless, achieving precise drug delivery to unknown disease sites using swarming micro/nanorobots remains a significant challenge. Here we develop a heterogeneous swarm comprising sensing microrobots (sensor-bots) and drug-carrying microrobots (carrier-bots) with collaborative tasking capabilities for precise drug delivery toward unknown sites. Leveraging robust interspecific hydrodynamic interactions, the sensor-bots and carrier-bots spontaneously synchronize and self-organize into stable heterogeneous microswarms. Given that the sensor-bots can create real-time pH maps employing pH-responsive structural-color changes and the doxorubicin-loaded carrier-bots exhibit selective adhesion to acidic targets via pH-responsive charge reversal, the sensor-carrier microswarm, when exploring unknown environments, can detect and localize uncharted acidic targets, guide itself to cover the area, and finally deploy therapeutic carrier-bots precisely there. This versatile platform holds promise for treating diseases with localized acidosis and inspires future theranostic microsystems with expandability, task flexibility, and high efficiency.
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Doxorrubicina , Sistemas de Liberación de Medicamentos , Doxorrubicina/química , Doxorrubicina/farmacología , Concentración de Iones de Hidrógeno , Acidosis , Humanos , Portadores de Fármacos/química , RobóticaRESUMEN
Micro/nanomotors (MNMs) are micro/nanoscale devices that can convert energy from their surroundings into autonomous motion. With this unique ability, they may revolutionize application fields ranging from active drug delivery to biological surgeries, environmental remediation, and micro/nanoengineering. To complete these applications, MNMs are required to have a vital capability to reach their destinations. Employing external fields to guide MNMs to the targets is common and effective way. However, in application scenarios where targets are generally unknown or dynamically change, MNMs must possess the capability of self-navigation or self-targeting. Taking advantage of tactic movements toward or away from signal sources, numerous intelligent MNMs with self-navigation or self-targeting have been demonstrated and attracted much attention during the past few years. In this Account, we elucidate the intelligent response mechanisms of such tactic MNMs, which are summarized as two main models. One is that local vector fields, including those of chemical concentration gradients, gravity, flows, and magnetic fields existing in systems, achieve the overall alignment of asymmetric MNMs via aligning torques, directing the MNMs to swim toward or away from the signal sources. Another is that isotropic MNMs may produce propulsion forces with direction solely determined by the local vector field regardless of their Brownian rotations. Then we discuss and highlight the recent progress in tactic MNMs, including chemotactic, phototactic, rheotactic, gravitactic, and magnetotactic motors. Artificial chemotactic MNMs can be designed with different morphologies and compositions if asymmetric reactions are associated with chemical concentration gradients. In these systems, asymmetric phoretic slip flows are induced, leading to torques that enable the anisotropic particles to align and exhibit chemotaxis. For phototactic MNMs, light irradiation establishes asymmetric fields surrounding the motors via light-induced chemical reactions or physical effects to generate phototactic motion. Shape-asymmetric MNMs reorient in natural fluid flows because of torques applied by the flows, inducing rheotactic movements. MNMs with either the centroid or magnetic components distributed asymmetrically maintain orientation under the torque triggered by gravity or magnetic forces, generating tactic motions. In the end, we envision the future development of synthetic tactic MNMs, including enhancement of the sensitivity of motors to target signals, increasing the diversity of chemical motor systems, and combining multiple mechanisms to endow the tactic motors with multiple functionality. By highlighting the current achievements and offering our perspective on tactic MNMs, we look forward to inspiring the emergence of the next generation of intelligent MNMs with taxis.
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Light, as an external stimulus, is capable of driving the motion of micro/nanomotors (MNMs) with the advantages of reversible, wireless and remote manoeuvre on demand with excellent spatial and temporal resolution. This review focuses on the state-of-the-art light-driven MNMs, which are able to move in liquids or on a substrate surface by converting light energy into mechanical work. The general design strategies for constructing asymmetric fields around light-driven MNMs to propel themselves are introduced as well as the photoactive materials for light-driven MNMs, including photocatalytic materials, photothermal materials and photochromic materials. Then, the propulsion mechanisms and motion behaviors of the so far developed light-driven MNMs are illustrated in detail involving light-induced phoretic propulsion, bubble recoil and interfacial tension gradient, followed by recent progress in the light-driven movement of liquid crystalline elastomers based on light-induced deformation. An outlook is further presented on the future development of light-driven MNMs towards overcoming key challenges after summarizing the potential applications in biomedical, environmental and micro/nanoengineering fields.
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Hybrid micromotors capable of both chemically powered propulsion and fuel-free light-driven actuation and offering built-in optical brakes for chemical propulsion are described. The new hybrid micromotors are designed by combining photocatalytic TiO2 and catalytic Pt surfaces into a Janus microparticle. The chemical reactions on the different surfaces of the Janus particle hybrid micromotor can be tailored by using chemical or light stimuli that generate counteracting propulsion forces on the catalytic Pt and photocatalytic TiO2 sides. Such modulation of the surface chemistry on a single micromotor leads to switchable propulsion modes and reversal of the direction of motion that reflect the tuning of the local ion concentration and hence the dominant propulsion force. An intermediate Au layer (under the Pt surface) plays an important role in determining the propulsion mechanism and operation of the hybrid motor. The built-in optical braking system allows "on-the-fly" control of the chemical propulsion through a photocatalytic reaction on the TiO2 side to counterbalance the chemical propulsion force generated on the Pt side. The adaptive dual operation of these chemical/light hybrid micromotors, associated with such control of the surface chemistry, holds considerable promise for designing smart nanomachines that autonomously reconfigure their propulsion mode for various on-demand operations.
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While chemical communication plays a key role in diverse natural processes, the intelligent chemical communication between synthetic nanomotors remains unexplored. The design and operation of bioinspired synthetic nanomotors is presented. Chemical communication between nanomotors is possible and has an influence on propulsion behavior. A chemical "message" is sent from a moving activator motor to a nearby activated (receiver) motor by release of Ag+ ions from a Janus polystyrene/Ni/Au/Ag activator motor to the activated Janus SiO2 /Pt nanomotor. The transmitted silver signal is translated rapidly into a dramatic speed change associated with the enhanced catalytic activity of activated motors. Selective and successive activation of multiple nanomotors is achieved by sequential localized chemical communications. The concept of establishing chemical communication between different synthetic nanomotors paves the way to intelligent nanoscale robotic systems that are capable of cooperating with each other.
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Compuestos Inorgánicos/química , Nanotecnología/instrumentación , Catálisis , Oro/química , Microscopía Electrónica de Transmisión , Movimiento (Física) , Níquel/química , Espectroscopía de Fotoelectrones , Plata/químicaRESUMEN
In this work, light-controlled bubble-propelled single-component metal oxide tubular microengines have for the first time been demonstrated. For such a simple single-component TiO2 tubular microengine in H2O2 aqueous solution under UV irradiation, when the inner diameter and length of the tube are regulated, the O2 molecules will nucleate and grow into bubbles preferentially on the inner concave surface rather than on the outer surface, resulting in a vital propulsion of the microengine. More importantly, the motion state and speed can be modulated reversibly, fast (the response time is less than 0.2 s) and wirelessly by adjusting UV irradiation. Consequently, the as-developed TiO2 tubular microengine promises potential challenged applications related to photocatalysis, such as "on-the-fly" photocatalytic degradation of organic pollutes and photocatalytic inactivation of bacteria due to the low cost, single component, and simple structure, as well as the facile fabrication in a large-scale.
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Micro/nanorobots (MNRs) are envisioned to provide revolutionary changes to therapies for infectious diseases as they can deliver various antibacterial agents or energies to many hard-to-reach infection sites. However, existing MNRs face substantial challenges in addressing complex infections that progress from superficial to deep tissues. Here, we develop swarming magnetic Fe3O4@polydopamine-tannic acid nanorobots (Fe3O4@PDA-TA NRs) capable of performing targeted bacteria elimination in complicated bacterial infections by integrating superficial photothermal and deep chemical strategies. The Fe3O4@PDA-TA nanoparticles (NPs), serving as building blocks of the nanorobots, are fabricated by in situ polymerization of dopamine followed by TA adhesion. When driven by alternating magnetic fields, Fe3O4@PDA-TA NPs can assemble into large energetic microswarms continuously flowing forward with tunable velocity. Thus, the swarming Fe3O4@PDA-TA NRs can be navigated to achieve rapid broad coverage of a targeted superficial area from a distance and rapidly eradicate bacteria residing there upon exposure to near-infrared (NIR) light due to their efficient photothermal conversion. Additionally, they can concentrate at deep infection sites by traversing through confined, narrow, and tortuous passages, exerting sustained antibacterial action through their surface TA-induced easy cell adhesion and subsequent membrane destruction. Therefore, the swarming Fe3O4@PDA-TA NRs show great potential for addressing complex superficial-to-deep infections. This study may inspire the development of future therapeutic microsystems for various diseases with multifunction synergies, task flexibility, and high efficiency.
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Individual differences in size, experience, and task specialization in natural swarms often result in heterogeneity and hierarchy, facilitating efficient and coordinated task accomplishment. Drawing inspiration from this phenomenon, a general strategy is proposed for organizing magnetic micro/nanorobots (MNRs) with apparent differences in size, shape, and properties into cohesive microswarms with tunable heterogeneity, controlled spatial hierarchy, and collaborative tasking capability. In this strategy, disparate magnetic MNRs can be manipulated to show reversible transitions between synchronization and desynchronization by elaborately regulating parameter sets of the rotating magnetic field. Utilizing these transitions, alongside local robust hydrodynamic interactions, diverse heterospecific pairings of disparate magnetic MNRs can be organized into heterogeneous microswarms, and their spatial organization can be dynamically adjusted from egalitarian to leader-follower-like hierarchies on the fly, both in open space and complex microchannels. Furthermore, when specializing the disparate MNRs with distinct functions ("division of labor") such as sensing and drug carrying, they can execute precise drug delivery targeting unknown sites in a collaborative sensing-navigating-cargo dropping sequence, demonstrating significant potential for precise tumor treatment. These findings highlight the critical roles of attribute differences and hierarchical organization in designing efficient swarming micro/nanorobots for biomedical applications.
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Robótica , Robótica/métodos , Humanos , Magnetismo/métodos , Nanotecnología/métodos , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Self-propelled chemical micro/nanomotors (MNMs) have demonstrated considerable potential in targeted drug delivery, (bio)sensing, and environmental remediation due to their autonomous nature and possible intelligent self-targeting behaviors (e.g., chemotaxis and phototaxis). However, these MNMs are commonly limited by their primary propulsion mechanisms of self-electrophoresis and electrolyte self-diffusiophoresis, making them prone to quenching in high electrolyte environments. Thus, the swarming behaviors of chemical MNMs in high-electrolyte media remain underexplored, despite their potential to enable the execution of complex tasks in high-electrolyte biological media or natural waters. In this study, we develop ultrasmall tubular nanomotors that exhibit ion-tolerant propulsions and collective behaviors. Upon vertical upward UV irradiation, the ultrasmall Fe2O3 tubular nanomotors (Fe2O3 TNMs) demonstrate positive superdiffusive photogravitaxis and can further self-organize into nanoclusters near the substrate in a reversible manner. After self-organization, the Fe2O3 TNMs exhibit a pronounced emergent behavior, allowing them to switch from random superdiffusions to ballistic motions near the substrate. Even at a high electrolyte concentration (Ce), the ultrasmall Fe2O3 TNMs retain a relatively thick electrical double layer (EDL) compared to their size, and the electroosmotic slip flow in their EDL is strong enough to propel them and induce phoretic interactions among them. As a result, the nanomotors can rapidly concentrate near the substrate and then gather into motile nanoclusters in high-electrolyte environments. This work opens a gate for designing swarming ion-tolerant chemical nanomotors and may expedite their applications in biomedicine and environmental remediation.
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In analogy to eukaryotic cells that move by beating the flagella, magnetically powered micro/nanorobots with flexible filaments are capable of eluding the limitation of the scallop theorem to generate net displacement in a three-dimensional space, but they are limited by complicated fabrication and low speed. Here, we demonstrate a tadpole-like flexible microswimmer with a head and tail that are both magnetic by developing a magnetically assisted in situ polymerization method. The flexible microswimmer consists of a magnetic-bead head fixed to a nanochain bundle of magnetic nanoparticles (tail), and the tail length and stiffness can be adjusted simply by changing the duration and strength of the applied magnetic field during fabrication, respectively. For the microswimmer under an oscillating magnetic field, the magnetic head generates an undulatory motion, which can be further increased by the flexible magnetic tail. The magnetically induced undulation of the head and tail generates a traveling wave propagating through its flexible tail, resulting in efficient tadpole-like propulsion of the microswimmer. The flexible microswimmer runs at a maximum motion speed when the tail length is â¼5 times the diameter of the magnetic head, corresponding to â¼half the wavelength of the undulatory motion. The flexible microswimmers reported here are promising for active sensing and drug delivery, as the tails can be designed with various responsive hydrogels, and the results are expected to advance flexible micro/nanorobots.
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Sistemas de Liberación de Medicamentos , Magnetismo , Animales , Larva , Campos Magnéticos , Movimiento (Física)RESUMEN
Biocompatible swarming magnetic nanorobots that work in blood vessels for safe and efficient targeted thrombolytic therapy in vivo are demonstrated. This is achieved by using magnetic beads elaborately grafted with heparinoid-polymer brushes (HPBs) upon the application of an alternating magnetic field B(t). Because of the dense surface charges bestowed by HPBs, the swarming nanorobots demonstrate reversible agglomeration-free reconfigurations, low hemolysis, anti-bioadhesion, and self-anticoagulation in high-ionic-strength blood environments. They are confirmed in vitro and in vivo to perform synergistic thrombolysis efficiently by "motile-targeting" drug delivery and mechanical destruction. Moreover, upon the completion of thrombolysis and removal of B(t), the nanorobots disassemble into dispersed particles in blood, allowing them to safely participate in circulation and be phagocytized by immune cells without apparent organ damage or inflammatory lesion. This work provides a rational multifaceted HPB biointerfacing design strategy for biomedical nanorobots and a general motile platform to deliver drugs for targeted therapies.
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Heparinoides , Polímeros , Sistemas de Liberación de Medicamentos , Terapia Trombolítica , Fenómenos MagnéticosRESUMEN
Through experiments and simulations, we show that fuel-free photoactive TiO2 microparticles can form mobile, coherent swarms in the presence of UV light, which track the subsequent movement of an irradiated spot in a fluid-filled microchamber. Multiple concurrent propulsion mechanisms (electrolyte diffusioosmotic swarming, photocatalytic expansion, and photothermal migration) control the rich collective behavior of the swarms, which provide a strategy to reversely manipulate cargo. The active swarms can autonomously pick up groups of inert particles, sort them by size, and sequentially release the sorted particles at particular locations in the microchamber. Hence, these swarms overcome three obstacles, limiting the utility of self-propelled particles. Namely, they can (1) undergo directed, long-range migration without the addition of a chemical fuel, (2) perform diverse collective behavior not possible with a single active particle, and (3) repeatedly and controllably isolate and deliver specific components of a multiparticle "cargo". Since light sources are easily fabricated, transported, and controlled, the results can facilitate the development of portable devices, providing broader access to the diagnostic and manufacturing advances enabled by microfluidics.
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Micro-/nanorobots (MNRs) are envisioned to act as "motile-targeting" platforms for biomedical tasks due to their ability to propel and navigate in challenging, hard-to-reach biological environments. However, it remains a great challenge for current swarming MNRs to accurately report and regulate therapeutic doses during disease treatment. Here we present the development of swarming multifunctional heater-thermometer nanorobots (HT-NRs) and their application in precise feedback photothermal hyperthermia delivery. The HT-NRs are designed as photothermal-responsive photonic nanochains consisting of magnetic Fe3O4 nanoparticles arranged periodically in one dimension and encapsulated in a temperature-responsive hydrogel shell. The HT-NRs exhibit energetic and controllable swarming motions under a rotating magnetic field, while simultaneously functioning as motile nanoheaters and nanothermometers, utilizing their photothermal conversion and (photo)thermal-responsive structural color changes (photothermochromism). Consequently, the HT-NRs can be quickly deployed to a remote target area (e.g., a superficial tumor lesion) using their collective motion and selectively eliminate diseased cells in a specific targeted region by utilizing their self-reporting photothermochromism as visual feedback for precisely regulating external light irradiation. This work may inspire the development of intelligent multifunctional theranostic micro-/nanorobots and their practical applications in precise disease treatment.
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Hipertermia Inducida , Termómetros , Retroalimentación , Temperatura , HidrogelesRESUMEN
Micro/nanorobots can propel and navigate in many hard-to-reach biological environments, and thus may bring revolutionary changes to biomedical research and applications. However, current MNRs lack the capability to collectively perceive and report physicochemical changes in unknown microenvironments. Here we propose to develop swarming responsive photonic nanorobots that can map local physicochemical conditions on the fly and further guide localized photothermal treatment. The RPNRs consist of a photonic nanochain of periodically-assembled magnetic Fe3O4 nanoparticles encapsulated in a responsive hydrogel shell, and show multiple integrated functions, including energetic magnetically-driven swarming motions, bright stimuli-responsive structural colors, and photothermal conversion. Thus, they can actively navigate in complex environments utilizing their controllable swarming motions, then visualize unknown targets (e.g., tumor lesion) by collectively mapping out local abnormal physicochemical conditions (e.g., pH, temperature, or glucose concentration) via their responsive structural colors, and further guide external light irradiation to initiate localized photothermal treatment. This work facilitates the development of intelligent motile nanosensors and versatile multifunctional nanotheranostics for cancer and inflammatory diseases.
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Traditional drug delivery systems opened the gate for tumor-targeted therapy, but they generally took advantage of enhanced permeability and retention or ligand-receptor mediated interaction, and thus suffered from limited recognition range (<0.5 nm) and low targeting efficiency (0.7%, median). Alternatively, micro/nanorobots (MNRs) may act as emerging "motile-targeting" drug delivery platforms to deliver therapeutic payloads, thereby making a giant step toward effective and safe cancer treatment due to their autonomous movement and navigation in biological media. This review focuses on the most recent developments of MNRs in "motile-targeting" drug delivery. After a brief introduction to traditional tumor-targeted drug delivery strategies and various MNRs, the representative applications of MNRs in "motile-targeting" drug delivery are systematically streamlined in terms of the propelling mechanisms. Following a discussion of the current challenges of each type of MNR in biomedical applications, as well as future prospects, several promising designs for MNRs that could benefit in "motile-targeting" drug delivery are proposed. This work is expected to attract and motivate researchers from different communities to advance the creation and practical application of the "motile-targeting" drug delivery platforms.
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"Life-like" nonequilibrium assemblies are of increasing significance, but suffering from limited steerability as they are generally based on micro/nanomotors with inherent asymmetry in chemical composition or geometry, of which the vigorous random Brownian rotations disturb the local interactions. Here, we demonstrate that isotropic photocatalytic micromotors, due to the persistent phoretic flow from the illuminated to shadowed side irrespective of their Brownian rotations, experience light-programmable local interactions (reversibly from attraction to repulsion and/or alignment) depending on the direction of the incident lights. Thus, they can be organized into a variety of tunable nonequilibrium assemblies, such as apolar solids (i.e., immobile colloidal crystal), polar liquids (i.e., phototactic colloidal stream), and polar solids (i.e., phototactic colloidal crystal), which can further be "cut" into a predesigned pattern by utilizing the switching motor-motor interactions at superimposed-light edges. This work facilitates the development of active matters and motile functional microdevices.
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Cargo delivery by micro/nanomotors provides enormous opportunities for micromanipulation, environmental cleaning, drug delivery, etc. However, due to the limited driving force, it is usually difficult for single micro/nanomotors to transport cargoes much larger or heavier than themselves. Here, we demonstrate that flocking phototactic TiO2 micromotors can cooperatively transport multiple and different types of large cargoes based on light-responsive diffusiophoresis. Utilizing spontaneous diffusiophoretic attraction, flocking TiO2 micromotors can load large cargoes. Under UV light navigation, flocking TiO2 micromotors cooperatively carry and transport cargoes via collective diffusiophoretic repulsion in open space or complex microenvironments. After reaching the destination, the carried cargoes can also be unloaded from the flock and be deployed at a predetermined destination by disassembling or reversing the flock. This study may pave the way for developing intelligent swarming micro/nanorobots for cooperative targeting micromanipulation and advancing their applications in drug delivery and microengineering.
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Synthetic chemotactic micro/nanomotors are envisioned to actively 'seek out' targets by following specific chemicals, but they are mainly powered by bioincompatible fuels and only show pseudochemotaxis (or advanced chemokinesis) due to their weak self-reorientation capabilities. Here we demonstrate that synthetic ZnO-based Janus micromotors can be powered by the alternative biocompatible fuel of CO2, and further provide the first example of self-reorientation-induced biomimetic chemotaxis using them. The ZnO-based micromotors are highly sensitive to dissolved CO2 in water, which enables the corrosion of ZnO to continuously occur by providing H+ through hydration. Thus, they can autonomously move even in water exposed to air based on self-diffusiophoresis. Furthermore, they can sense the local CO2 gradient and perform positive chemotaxis by self-reorientations under the phoretic torque. Our discovery opens a gate to developing intelligent micro/nanomotors powered by, and sensitive to, biocompatible atmospheric or endogenous gaseous chemicals for biomedical and environmental applications.
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We present a simple and effective nonequilibrium heat-treatment approach that allows for the facile fabrication of maghemite (γ-Fe(2)O(3)) fiber-in-tube and tube-in-tube nanostructures by heat-treating electrospun precursor fibers composed of polyvinylpyrrolidone (PVP) and iron citrate with a carefully devised heating rate (R). In this nonequilibrium heat-treatment procedure, R can be easily utilized to tune the temperature gradient established in the inner portion of the fibers and the difference between the cohesive force and the adhesive force at the interface layer between the inner gel and the dense rigid shell generated in situ by a high R. Therefore, the contraction direction of the precursor nanofibers and the final morphology of the resultant γ-Fe(2)O(3) fibers ranging from a simple tube to a fiber in tube to a tube in tube are realized for control. The nonequilibrium heat-treatment approach reported here can be readily extended to the fabrication of other materials with controllable interior structures by fast heating their corresponding gel precursors, which may be fabricated on the basis of electrospinning techniques and others. The resultant γ-Fe(2)O(3) fiber-in-tube and tube-in-tube nanostructures may have important applications in a number of areas, such as magnetic separable catalysts or catalyst supporting materials, sensors, absorbents, microreactors, and so forth, because of their structural characteristics and good magnetic properties.