All-Optical Trapping and Programmable Transport of Gold Nanorods with Simultaneous Orientation and Spinning Control.

Gold nanorods (GNRs) are of special interest in nanotechnology and biomedical applications due to their biocompatibility, anisotropic shape, enhanced surface area, and tunable optical properties. The use of GNRs, for example, as sensors and mechanical actuators, relies on the ability to remotely control their orientation as well as their translational and rotational motion, whether individually or in groups. Achieving such particle control by using optical tools is challenging and exceeds the capabilities of conventional laser tweezers. We present a tool that addresses this complex manipulation problem by using a curve-shaped laser trap, enabling the optical capture and programmable transport of single and multiple GNRs along any trajectory. This type of laser trap combines confinement and propulsion optical forces with optical torque to transport the GNRs while simultaneously controlling their rotation (spinning) and orientation. The proposed system facilitates the light-driven control of GNRs and the quantitative characterization of their motion dynamics including transport speed, spinning frequency, orientation, and confinement strength. We experimentally demonstrate that remote control of the GNRs can be achieved both near a substrate surface (2D trapping) and deep within the sample (3D all-optical trapping). The motion dynamics of two sets of off-resonant GNRs, possessing similar aspect ratios but different resonance wavelengths, are analyzed to highlight the role played by their optical and mechanical properties in the optical manipulation process. The experimental results are supported by a theoretical model describing the observed motion dynamics of the GNRs. This optical manipulation tool can significantly facilitate applications of light-driven nanorods.

Fe3O4 nanomotors loaded with siRNA are used for tumor therapy.

Excessive iron ion accumulation in cells can trigger apoptosis; however, the balance of iron ions in cells minimizes the effect of excessive iron accumulation. Here, we report a biocompatible nanomotor that reduces the ability of cells to clear iron ions using loaded siRNA. First, catalase and polydopamine were loaded onto Fe3O4 particles by layer-by-layer self-assembly technology to endow the particles with a self-propulsion ability. A nanomotor (NP-siRNA) loaded with siRNA was then prepared by electrostatic action. Nanoparticles (NP) can achieve self-actuation in an aqueous solution with a magnetic field and H2O2 and have good movement ability in water, PBS, and FBS solutions, resulting in greater contact with tumor cells. The results show that the nanomotor has good in vivo and in vitro anti-tumor effects, and good biocompatibility.

Construction of Yolk@shell Nanocomposite Particles with Controlled Multisized Pore Structures by Monomicelle Confined Assembly.

Hollow nanoparticles with tunable structures and spatial and chemical specificity are considered as promising carriers. However, it remains a formidable challenge to endow hollow nanomaterials with precisely controlled multisized macro/mesoporous structures up to now. This paper demonstrates a "polydopamine (PDA) expansion-shrinkage" strategy combined with a monomicelle interfacial confined assembly method to achieve the highly controllable preparation of a series of yolk@shell PDA@SiO2 composite nanoparticles with structural asymmetry and a tunable multisized pore in the shell. The strategy allows systematic manipulation of the average pore size of large slit pores in the range of 15.4-86.5 nm by adjusting the reaction temperature. Benefiting from advantages such as an asymmetric structure and multilevel porosity, they exhibit excellent performance in the applications of on-demand loading of dual-sized cargoes, dual-propelled nanomotors, and particle size-selected encapsulation and separation. These findings provide inspiration for the construction of asymmetric yolk@shell structures with tunable multisized pores for a wide range of biological and chemical applications.

A mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery.

Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.

Orbits, Spirals, and Trapped States: Dynamics of a Phoretic Janus Particle in a Radial Concentration Gradient.

A long-standing goal in colloidal active matter is to understand how gradients in fuel concentration influence the motion of phoretic Janus particles. Here, we present a theoretical description of the motion of a spherical phoretic Janus particle in the presence of a radial gradient of the chemical solute driving self-propulsion. Radial gradients are a geometry relevant to many scenarios in active matter systems and naturally arise due to the presence of a point source or sink of fuel. We derive an analytical solution for the Janus particle's velocity and quantify the influence of the radial concentration gradient on the particle's trajectory. Compared to a phoretic Janus particle in a linear gradient in fuel concentration, we uncover a much richer set of dynamic behaviors including circular orbits and trapped stationary states. We identify the ratio of the phoretic mobilities between the two domains of the Janus particle as a central quantity in tuning their dynamics. Our results provide a path for developing optimum protocols for tuning the dynamics of phoretic Janus particles and mixing fluid at the microscale. In addition, this work suggests a method for quantifying the surface properties of phoretic Janus particles, which have proven to be challenging to probe experimentally.

Mechanical Efficiency of Photochromic Nanomotors, From First Principles.

Photochromic molecular motors hold promise for a multitude of potential applications in fields ranging from medicine to communications and structural repair. Yet, it is still a challenge to predict their mechanical efficiency. Here, azobenzene is explored as a representative light-driven nanomotor and estimate its quantum yield of photoisomerization and maximum mechanical efficiency. This is based on first-principles mapping of the 3D potential energy surfaces for the ground and excited states of the trans and cis configurations and identifying the minimum energy pathway for isomerization. A work cycle is devised and identifies force constant as the parameter that resembles temperature in the Carnot heat engine, but with very different efficiencies. The results show that the optomechanical efficiency of azobenzene at constant load is about 5% albeit under ideal conditions. To test the hypothesis, the study also explores the optomechanical efficiency of stilbene and 2-butene and shows that their efficiency does not exceed 5%.

Hibernating/Awakening Nanomotors Promote Highly Efficient Cryopreservation by Limiting Ice Crystals.

The disruptions caused by ice crystal formation during the cryopreservation of cells and tissues can cause cell and tissue damage. Thus, preventing such damage during cryopreservation is an important but challenging goal. Here, a hibernating/awakening nanomotor with magnesium/palladium covering one side of a silica platform (Mg@Pd@SiO2) is proposed. This nanomotor is used in the cultivation of live NCM460 cells to demonstrate a new method to actively limit ice crystal formation and enable highly efficient cryopreservation. Cooling Mg@Pd@SiO2 in solution releases Mg2+/H2 and promotes the adsorption of H2 at multiple Pd binding sites on the cell surface to inhibit ice crystal formation and cell/tissue damage; additionally, the Pd adsorbs and stores H2 to form a hibernating nanomotor. During laser-mediated heating, the hibernating nanomotor is activated (awakened) and releases H2, which further suppresses recrystallization and decreases cell/tissue damage. These hibernating/awakening nanomotors have great potential for promoting highly efficient cryopreservation by inhibiting ice crystal formation.

An NIR-propelled janus nanomotor with enhanced ROS-scavenging, immunomodulating and biofilm-eradicating capacity for periodontitis treatment.

Periodontitis is an inflammatory disease caused by bacterial biofilms, which leads to the destruction of periodontal tissue. Current treatments, such as mechanical cleaning and antibiotics, struggle to effectively address the persistent biofilms, inflammation, and tissue damage. A new approach involves developing a Janus nanomotor (J-CeM@Au) by coating cerium dioxide-doped mesoporous silica (CeM) with gold nanoparticles (AuNPs). This nanomotor exhibits thermophoretic motion when exposed to near-infrared (NIR) laser light due to the temperature gradient produced by the photothermal effects of asymmetrically distributed AuNPs. The NIR laser provides the energy for propulsion and activates the nanomotor's antibacterial properties, allowing it to penetrate biofilms and kill bacteria. Additionally, the nanomotor's ability to scavenge reactive oxygen species (ROS) can modulate the immune response and create a regenerative environment, promoting the healing of periodontal tissue. Overall, this multifunctional nanomotor offers a promising new approach for treating periodontitis by simultaneously addressing biofilm management and immune modulation with autonomous movement.

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.

Unveiling Hidden Hyperuniformity: Radial Turing Pattern Formation of Marangoni-Driven SiO2 Nanoparticles on Liquid Metal Surface.

Mastering the self-organization of nanoparticle morphologies is pivotal in soft matter physics and film growth. Silicon dioxide (SiO2) nanoparticles are an archetypical model of nanomotor in soft matter. Here, the emphasis is on the self-organizing behavior of SiO2 nanoparticles under extreme conditions. It is unveiled that manipulating the states of the metal substrate profoundly dictates the motion characteristics of SiO2 nanoparticles. This manipulation triggers the emergence of intricate morphologies and distinctive patterns. Employing a reaction-diffusion model, the fundamental roles played by Brownian motion and Marangoni-driven motion in shaping fractal structures and radial Turing patterns are demonstrated, respectively. Notably, these radial Turing patterns showcase hyperuniform order, challenging conventional notions of film morphology. These discoveries pave the way for crafting non-equilibrium morphological materials, poised with the potential for self-healing, adaptability, and innovative applications.

NIR-II Light-Actuated Nanomotors for Enhanced Photoimmunotherapy Toward Hepatocellular Carcinoma.

Light-propelled nanomotors, which can convert external light into mechanical motion, have shown considerable potential in the construction of a new generation of drug delivery systems. However, the therapeutic efficacy of light-driven nanomotors is always unsatisfactory due to the limited penetration depth of near-infrared-I (NIR-I) light and the inherent biocompatibility of the motor itself. Herein, an asymmetric nanomotor (Pd@ZIF-8/R848@M JNMs) with efficient motion capability is successfully constructed for enhanced photoimmunotherapy toward hepatocellular carcinoma. Under near-infrared-II (NIR-II) irradiation, Pd@ZIF-8/R848@M JNMs convert light energy into heat energy, exhibiting self-thermophoretic locomotion to penetrate deeper into tumor tissues to achieve photothermal therapy. At the same time, functionalized with an immune-activated agent Resiquimod (R848), our nanomotors could convert a "cold tumor" into a "hot tumor", transforming the immunosuppressive microenvironment into an immune-activated state, thus achieving immunotherapy. Dual photoimmunotherapy of the as-developed NIR-II light-driven Pd@ZIF-8/R848@M JNMs demonstrates considerable tumor inhibition effects, offering a promising therapeutic approach in the field of anticancer therapy.

Recent advances in the development of tumor microenvironment-activatable nanomotors for deep tumor penetration.

Cancer represents a significant threat to human health, with the use of traditional chemotherapy drugs being limited by their harsh side effects. Tumor-targeted nanocarriers have emerged as a promising solution to this problem, as they can deliver drugs directly to the tumor site, improving drug effectiveness and reducing adverse effects. However, the efficacy of most nanomedicines is hindered by poor penetration into solid tumors. Nanomotors, capable of converting various forms of energy into mechanical energy for self-propelled movement, offer a potential solution for enhancing drug delivery to deep tumor regions. External force-driven nanomotors, such as those powered by magnetic fields or ultrasound, provide precise control but often necessitate bulky and costly external equipment. Bio-driven nanomotors, propelled by sperm, macrophages, or bacteria, utilize biological molecules for self-propulsion and are well-suited to the physiological environment. However, they are constrained by limited lifespan, inadequate speed, and potential immune responses. To address these issues, nanomotors have been engineered to propel themselves forward by catalyzing intrinsic "fuel" in the tumor microenvironment. This mechanism facilitates their penetration through biological barriers, allowing them to reach deep tumor regions for targeted drug delivery. In this regard, this article provides a review of tumor microenvironment-activatable nanomotors (fueled by hydrogen peroxide, urea, arginine), and discusses their prospects and challenges in clinical translation, aiming to offer new insights for safe, efficient, and precise treatment in cancer therapy.

NIR-II light-powered core-shell prodrug nanomotors enhance cancer therapy through synergistic oxidative stress-photothermo modulation.

Near-infrared-II (NIR-II) photothermal therapy is emerging as a cutting-edge modality for tumor ablation due to its good biosafety, high penetration ability and spatiotemporal controllability. Despite efforts, establishing a link between cellular metabolic regulation and photothermal performance is still promising in synergistic cancer therapy. Herein, we developed a core-shell semiconducting polymer@metal-phenolic network (SP@GFP) nanomotor by assembling diphenol-terminated cisplatin prodrug ligand (cPt-DA) and iron (III) (Fe3+) through metal coordination on SP particles in the presence of GOx and DSPE-PEG-cRGD, for NIR-II-propelled self-propulsion and synergistic cancer therapy. Remotely driving the SP@GFP nanomotor with an NIR-II laser through a thermophoresis mechanism would allow for in-depth penetration and accumulation. The synergistic photothermal effect and continuous Fe2+-mediated ROS generation of SP@GFP nanomotor could activate photothermal, chemotherapeutic effects and ferroptosis pathway for cancer cells through reshaping cellular metabolic pathways (HSP and GPX4). By combining the concepts of chemotherapeutic prodrugs, catalytic ROS generation, photothermal response and cellular metabolic regulation, the NIR-II laser-controlled core-shell SP@GFP nanomotor displayed improved outcomes for enhanced cancer therapy through synergistic oxidative stress-photothermo modulation. STATEMENT OF SIGNIFICANCE.

Nanogel-based nitric oxide-driven nanomotor for deep tissue penetration and enhanced tumor therapy.

Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.

Catalase-Powered Nanobots for Overcoming the Mucus Barrier.

Biological barriers present a significant obstacle to treatment, especially when drugs are administered locally to increase their concentrations at the target site while minimizing unintended off-target effects. Among these barriers, mucus presents a challenge, as it serves as a protective layer in the respiratory, urogenital, and gastrointestinal tracts. Its role is to shield the underlying epithelial cells from pathogens and toxic compounds but also impedes the efficient delivery of drugs. Despite the exploration of mucolytic agents to improve drug delivery, overcoming this protective barrier remains a significant hurdle. In our study, we investigate an alternative approach involving the use of catalase-powered nanobots. We use an in vitro model that simulates intestinal mucus secretion to demonstrate the dual functionality of our nanobots. This includes their ability to disrupt mucus, which we confirmed through in vitro and ex vivo validation, as well as their self-propulsion to overcome the mucus barrier, resulting in a 60-fold increase compared with passive nanoparticles. Therefore, our findings highlight the potential utility of catalase-powered nanobots as carriers for therapeutic agents since they could enhance drug delivery efficiency by penetrating the mucus barrier.

Light-driven rGO/Cu2 + 1O tubular nanomotor with active targeted drug delivery for combination treatment of cancer cells.

The unprecedented navigation ability in micro/nanoscale and tailored functionality tunes micro/nanomotors as new target drug delivery systems, open up new horizons for biomedical applications. Herein, we designed a light-driven rGO/Cu2 + 1O tubular nanomotor for active targeting of cancer cells as a drug delivery system. The propulsion performance is greatly enhanced in real cell media (5% glucose cells isotonic solution), attributing to the introduction of oxygen vacancy and reduced graphene oxide (rGO) layer for separating photo-induced electron-hole pairs. The motion speed and direction can be readily modulated. Meanwhile, doxorubicin (DOX) can be loaded quickly on the rGO layer because of π-π bonding effect. The Cu2 + 1O matrix in the tiny robots not only serves as a photocatalyst to generate a chemical concentration gradient as the driving force but also acts as a nanomedicine to kill cancer cells as well. The strong propulsion of light-driven rGO/Cu2 + 1O nanomotors coupled with tiny size endow them with active transmembrane transport, assisting DOX and Cu2 + 1O breaking through the barrier of the cell membrane. Compared with non-powered nanocarrier and free DOX, light-propelled rGO/Cu2 + 1O nanomotors exhibit greater transmembrane transport efficiency and significant therapeutic efficacy. This proof-of-concept nanomotor design presents an innovative approach against tumor, enlarging the list of biomedical applications of light-driven micro/nanomotors to the superficial tissue treatment.

Chemically Powered Nanomotors with Magnetically Responsive Function for Targeted Delivery of Exosomes.

Janus structure plays a crucial role in achieving chemically driven nanomotors with exceptional motion performance. However, Janus-structured chemically driven nanomotors with magnetic responsiveness are commonly fabricated by sputtering metal films. In the study, a self-assembly technique is employed to asymmetrically modify the surfaces of magnetic silica (SiO2@Fe3O4) nanoparticles with platinum nanoparticles, resulting in the formation of this kind nanomotors. Compared to platinum film, platinum nanoparticles exhibit a larger surface area and a higher catalytic activity. Hence, the nanomotors demonstrate improved diffusion capabilities at a significantly lower concentration (0.05%) of hydrogen peroxide (H2O2). Meanwhile, exosomes have gained attention as a potential tool for the efficient delivery of biological therapeutic drugs due to their biocompatibility. However, the clinical applications of exosomes are limited by their restricted tropism. The previously obtained nanomotors are utilized to deliver exosomes, greatly enhancing its targetability. The drug doxorubicin (DOX) is subsequently encapsulated within exosomes, acting as a representative drug model. Under the conditions of H2O2 concentration at the tumor site, the exosomes exhibited a significantly enhanced rate of entry into the breast cancer cells. The utilization of the nanomotors for exosomes presents a novel approach in the development of hybrid chemically and magnetically responsive nanomotors.

Inorganic catalase-powered nanomotors with hyaluronic acid coating for pneumonia therapy.

Clinical therapy for widespread infections caused by Streptococcus pneumoniae (S. pneumoniae), such as community-acquired pneumonia, is highly challenging. As an important bacterial toxin, hydrogen peroxide (H2O2) secreted by S. pneumoniae can suppress the host's immune system and cause more severe disease. To address this problem, a hyaluronic acid (HA)-coated inorganic catalase-driven Janus nanomotor was developed, which can cleverly utilize and decompose H2O2 to reduce the burden of bacterial infection, and have excellent drug loading capacity. HA coating prevents rapid leakage of loaded antibiotics and improves the biocompatibility of the nanomaterials. The Janus nanomotor converted H2O2 into oxygen (O2), gave itself the capacity to move actively, and encouraged widespread dispersion in the lesion site. Encouragingly, animal experiments demonstrated that the capability of the nanomotors to degrade H2O2 contributes to diminishing the proliferation of S. pneumoniae and lung tissue damage. This self-propelled drug delivery platform provides a new therapeutic strategy for infections with toxin-secreting bacteria.

Boosting the Efficiency of Photoactive Rod-Shaped Nanomotors via Magnetic Field-Induced Charge Separation.

Photocatalytic nanomotors have attracted a lot of attention because of their unique capacity to simultaneously convert light and chemical energy into mechanical motion with a fast photoresponse. Recent discoveries demonstrate that the integration of optical and magnetic components within a single nanomotor platform offers novel advantages for precise motion control and enhanced photocatalytic performance. Despite these advancements, the impact of magnetic fields on energy transfer dynamics in photocatalytic nanomotors remains unexplored. Here, we introduce dual-responsive rod-like nanomotors, made of a TiO2/NiFe heterojunction, able to (i) self-propel upon irradiation, (ii) align with the direction of an external magnetic field, and (iii) exhibit enhanced photocatalytic performance. Consequently, when combining light irradiation with a homogeneous magnetic field, these nanomotors exhibit increased velocities attributed to their improved photoactivity. As a proof-of-concept, we investigated the ability of these nanomotors to generate phenol, a valuable chemical feedstock, from benzene under combined optical and magnetic fields. Remarkably, the application of an external magnetic field led to a 100% increase in the photocatalytic phenol generation in comparison with light activation alone. By using various state-of-the-art techniques such as photoelectrochemistry, electrochemical impedance spectroscopy, photoluminescence, and electron paramagnetic resonance, we characterized the charge transfer between the semiconductor and the alloy component, revealing that the magnetic field significantly improved charge pair separation and enhanced hydroxyl radical generation. Consequently, our work provides valuable insights into the role of magnetic fields in the mechanisms of light-driven photocatalytic nanomotors for designing more effective light-driven nanodevices for selective oxidations.

Sunlight-triggered prebiotic nanomotors for inhibition and elimination of pathogen and biofilm in aquatic environment.

Pathogen contamination in drinking water sources causes waterborne infectious diseases, seriously threatening human health. Nowadays, stimuli-responsive self-propelled nanomotors are appealing therapeutic agents for antibacterial therapy in vivo. However, achieving water disinfection using these nanobots is still a great challenge. Herein, we report on prebiotic galactooligosaccharide-based nanomotors for sunlight-regulated water disinfection. The nanomotors can utilize galactooligosaccharide-based N-nitrosamines as sunlight-responsive fuels for the spontaneous production of antibacterial nitric oxide. Such a solar-to-chemical energy conversion would power the nanomotors for self-diffusiophoresis, which could promote the diffusion of the nanomotors in water and their penetration in the biofilm, significantly enhancing the inhibition and elimination of the pathogens and their biofilms in aquatic environments. After water treatments, the prebiotic-based residual disinfectants can be selectively utilized by beneficial bacteria to effectively relieve safety risks to the environment and human health. The low-energy-cost, green and potent antibacterial nanobots show promising potential in water disinfection.