Temperature-Sensitive Polymer-Driven Nanomotors for Enhanced Tumor Penetration and Photothermal Therapy.

Self-propelled nanomotors possess strong propulsion and penetration abilities, which can increase the efficiency of cellular uptake of nanoparticles and enhance their cytotoxicity against tumor cells, opening a new path for treating major diseases. In this study, the concept of driving nanomotors by alternately stretching and contracting a temperature-sensitive polymer (TS-P) chain is proposed. The TS-Ps are successfully linked to one side of Cu2-xSe@Au (CS@Au) nanoparticles to form a Janus structure, which is designated as Cu2-xSe@Au-polymer (CS@Au-P) nanomotors. Under near-infrared (NIR) light irradiation, Cu2-xSe nanoparticles generate photothermal effects that change the system temperature, triggering the alternation of the TS-P structure to generate a mechanical force that propels the motion of CS@Au-P nanomotors. The nanomotor significantly improved the cellular uptake of nanoparticles and enhanced their penetration and accumulation in tumor. Furthermore, the exceptional photothermal conversion efficiency of CS@Au-P nanomotors suggests their potential as nanomaterials for photothermal therapy (PTT). The prepared material exhibited good biocompatibility and anti-tumor effects both in vivo and in vitro, providing new research insights into the design and application of nanomotors in tumor therapy.

Acidity-Actuated Polymer/Calcium Phosphate Hybrid Nanomotor (PCaPmotor) for Penetrating Drug Delivery and Synergistic Anticancer Immunotherapy.

Tumor acidity-driven nanomotors may offer robust propulsion for tumor-specific penetrating drug delivery. Herein, an acidity-actuated poly(amino acid) calcium phosphate (CaP) hybrid nanomotor (PCaPmotor) was designed, using a mPEG-PAsp-PPhe@THZ531 micelle (Poly@THZ) for CaP mineralization accompanied by αPD-L1 antibody encapsulation. Dissolution of the CaP layer in an acidic tumor environment gave off heat energy to propel the nanomotor to augment the cellular uptake and penetration into deeply seated cancer cells while facilitating αPD-L1 release. THZ531 delivered by the PCaPmotor inhibited CDK12 and its down-streamed phosphorylation of RNAP-II to increase the cancer immunogenicity events such as the DNA damage, cell apoptosis, immunogenic cell death, lysosomal function disturbance, and MHC-I upregulation. THZ531 and αPD-L1 cosupplied by PCaPmotor significantly increased the frequency of DCs maturation and intratumoral infiltration of CTLs, but the two free drugs did not. Consequently, the PCaP@THZ/αPD-L1 nanomotor resulted in synergistic anticancer immunotherapy in mice. This acid-actuated PCaPmotor represented a new paradigm for penetrating drug delivery.

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.

Hyaluronic acid-targeted dual-bubble/photothermal-driven nanomissile for enhanced "four-in-one" anti-tumor strategy.

The dense extracellular matrix and high interstitial pressure affect the diffusion of nanodrug in tumor tissue, resulting in a small range of action of the active components in nanodrug, thereby affecting its anticancer efficacy. In order to enhance the diffusion ability of nanodrug, a dual-bubble/photothermal-driven nanomissile (HA@MnO2@TA/Fe/ICG/TPZ, HMTAFIT) was designed through "four in one" anti-tumor strategy. Harnessing the capabilities of hyaluronic acid, a biomacromolecule, the nanomotor transforms into a nanomissile, targeting cancer cells with precision. The oxygen generated by the reaction of manganese dioxide with hydrogen peroxide and the local temperature rise of indocyanine green under near-infrared light endow HMTAFIT with the ability of bubble/photothermal dual-driven, and the outermost layer of modified hyaluronic acid incubates the targeting properties of HMTAFIT which could avoid damage to normal cells. The bubble/photothermal-dual-driven increases motion speed of HMTAFIT by 13.8 µm/s, and the enhanced "four in one" anti-tumor strategy effectively improved the anticancer efficacy. The precision-guided nanomissile boasts the capability to eliminate deep-seated cancer cells and overcome multidrug resistance via optimized diffusion and a cutting-edge "four-in-one" approach.

Bottle Nanomotors Amplify Tumor Oxidative Stress for Enhanced Calcium Overload/Chemodynamic Therapy.

Developing multifunctional, stimuli-responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO2 and MnO. Under acidic TME, CaO2 reacts with acid to release Ca2+ to induce mitochondrial damage and simultaneously produces O2 and H2O2, when the loaded MnO exerts Fenton-like activity to produce ·OH and O2 based on the produced H2O2. The generated O2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca2 + overloading, GSH depletion induced by Mn2+, and Mn2+ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.

Micro/Nanomotor-Driven Intelligent Targeted Delivery Systems: Dynamics Sources and Frontier Applications.

Micro/nanomotors represent a promising class of drug delivery carriers capable of converting surrounding chemical or external energy into mechanical power, enabling autonomous movement. Their distinct autonomous propulsive force distinguishes them from other carriers, offering significant potential for enhancing drug penetration across cellular and tissue barriers. A comprehensive understanding of micro/nanomotor dynamics with various power sources is crucial to facilitate their transition from proof-of-concept to clinical application. In this review, micro/nanomotors are categorized into three classes based on their energy sources: endogenously stimulated, exogenously stimulated, and live cell-driven. The review summarizes the mechanisms governing micro/nanomotor movements under these energy sources and explores factors influencing autonomous motion. Furthermore, it discusses methods for controlling micro/nanomotor movement, encompassing aspects related to their structure, composition, and environmental factors. The remarkable propulsive force exhibited by micro/nanomotors makes them valuable for significant biomedical applications, including tumor therapy, bio-detection, bacterial infection therapy, inflammation therapy, gastrointestinal disease therapy, and environmental remediation. Finally, the review addresses the challenges and prospects for the application of micro/nanomotors. Overall, this review emphasizes the transformative potential of micro/nanomotors in overcoming biological barriers and enhancing therapeutic efficacy, highlighting their promising clinical applications across various biomedical fields.

Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits.

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO2 nanospheres with Cu2O nanoblocks. The resulting CaO2-Cu2O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO2-Cu2O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g., Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g., Prevotellaceae and Helicobacter). Our gas-driven CaO2-Cu2O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

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.

Black Titania Janus Mesoporous Nanomotor for Enhanced Tumor Penetration and Near-Infrared Light-Triggered Photodynamic Therapy.

Thanks to their excellent photoelectric characteristics to generate cytotoxic reactive oxygen species (ROS) under the light-activation process, TiO2 nanomaterials have shown significant potential in photodynamic therapy (PDT) for solid tumors. Nevertheless, the limited penetration depth of TiO2-based photosensitizers and excitation sources (UV/visible light) for PDT remains a formidable challenge when confronted with complex tumor microenvironments (TMEs). Here, we present a H2O2-driven black TiO2 mesoporous nanomotor with near-infrared (NIR) light absorption capability and autonomous navigation ability, which effectively enhances solid tumor penetration in NIR light-triggered PDT. The nanomotor was rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of a NIR light-responsive black TiO2 nanosphere and an enzyme-modified periodic mesoporous organosilica (PMO) nanorod that wraps around the TiO2 nanosphere. The overexpressed H2O2 can drive the nanomotor in the TME under catalysis of catalase in the PMO domain. By precisely controlling the ratio of TiO2 and PMO compartments in the Janus nanostructure, TiO2&PMO nanomotors can achieve optimal self-propulsive directionality and velocity, enhancing cellular uptake and facilitating deep tumor penetration. Additionally, by the decomposition of endogenous H2O2 within solid tumors, these nanomotors can continuously supply oxygen to enable highly efficient ROS production under the NIR photocatalysis of black TiO2, leading to intensified PDT effects and effective tumor inhibition.

Nanoscopic Imaging of Self-Propelled Ultrasmall Catalytic Nanomotors.

Ultrasmall nanomotors (<100 nm) are highly desirable nanomachines for their size-specific advantages over their larger counterparts in applications spanning nanomedicine, directed assembly, active sensing, and environmental remediation. While there are extensive studies on motors larger than 100 nm, the design and understanding of ultrasmall nanomotors have been scant due to the lack of high-resolution imaging of their propelled motions with orientation and shape details resolved. Here, we report the imaging of the propelled motions of catalytically powered ultrasmall nanomotors─hundreds of them─at the nanometer resolution using liquid-phase transmission electron microscopy. These nanomotors are Pt nanoparticles of asymmetric shapes ("tadpoles" and "boomerangs"), which are colloidally synthesized and observed to be fueled by the catalyzed decomposition of NaBH4 in solution. Statistical analysis of the orientation and position trajectories of fueled and unfueled motors, coupled with finite element simulation, reveals that the shape asymmetry alone is sufficient to induce local chemical concentration gradient and self-diffusiophoresis to act against random Brownian motion. Our work elucidates the colloidal design and fundamental forces involved in the motions of ultrasmall nanomotors, which hold promise as active nanomachines to perform tasks in confined environments such as drug delivery and chemical sensing.

Self-propelled enzyme-controlled IR-mesoporous silica Janus nanomotor for smart delivery.

Here, we report the preparation of a novel Janus nanoparticle with opposite Ir and mesoporous silica nanoparticles through a partial surface masking with toposelective modification method. This nanomaterial was employed to construct an enzyme-powered nanomachine with self-propulsion properties for on-command delivery. The cargo-loaded nanoparticle was provided with a pH-sensitive gate and unit control at the mesoporous face by first attaching boronic acid residues and further immobilization of glucose oxidase through reversible boronic acid esters with the carbohydrate residues of the glycoenzyme. Addition of glucose leads to the enzymatic production of H2O2 and gluconic acid, being the first compound catalytically decomposed at the Ir nanoparticle face producing O2 and causing the nanomachine propulsion. Gluconic acid leads to a pH reduction at the nanomachine microenvironment causing the disruption of the gating mechanism with the subsequent cargo release. This work demonstrates that enzyme-mediated self-propulsion improved release efficiency being this nanomotor successfully employed for the smart release of Doxorubicin in HeLa cancer cells.

H2S-Powered Nanomotors for Active Therapy of Tumors by Inducing Ferroptosis and Lactate-Pyruvate Axis Disorders.

Disruption of the symbiosis of extra/intratumoral metabolism is a good strategy for treating tumors that shuttle resources from the tumor microenvironment. Here, we report a precision treatment strategy for enhancing pyruvic acid and intratumoral acidosis to destroy tumoral metabolic symbiosis to eliminate tumors; this approach is based on PEGylated gold and lactate oxidase-modified aminated dendritic mesoporous silica with lonidamine and ferrous sulfide loading (PEG-Au@DMSNs/FeS/LND@LOX). In the tumor microenvironment, LOX oxidizes lactic acid to produce pyruvate, which represses tumor cell proliferation by inhibiting histone gene expression and induces ferroptosis by partial histone monoubiquitination. In acidic tumor conditions, the nanoparticles release H2S gas and Fe2+ ions, which can inhibit catalase activity to promote the Fenton reaction of Fe2+, resulting in massive ·OH production and ferroptosis via Fe3+. More interestingly, the combination of H2S and LND (a monocarboxylic acid transporter inhibitor) can cause intracellular acidosis by lactate, and protons overaccumulate in cells. Multiple intracellular acidosis is caused by lactate-pyruvate axis disorders. Moreover, H2S provides motive power to intensify the shuttling of nanoparticles in the tumor region. The findings confirm that this nanomedicine system can enable precise antitumor effects by disrupting extra/intratumoral metabolic symbiosis and inducing ferroptosis and represents a promising active drug delivery system candidate for tumor treatment.

Thermal accelerated urease-driven hyaluronan-targeted melanin nano-missile for bio-radar detection and chemodrug-free phototherapy.

Polymer-based nanomotors are attracting increasing interest in the biomedical field due to their microscopic size and kinematic properties which support overcoming biological barriers, completing cellular uptake and targeted blasting in limited spaces. However, their applications are limited by the complex viscous physiological environment and lack of sufficient biocompatibility. This manuscript firstly reports a natural melanin nano-missile of MNP@HA-EDA@Urease@AIE PS (MHUA) based on photothermally accelerated urease-driven to achieve chemodrug-free phototherapy. Compared to conventional nano-missiles that only provide driving force, this photothermally accelerated urease-driven nanomotor is independent of chemodrug to maximise biocompatibility, and achieve ideal therapeutic effect through targeted PTT/PDT. In particular, the thermal effect can not only boost the catalytic activity of urease but also achieve ideally anti-tumor effect. In addition, guided by and AIE PS, the nanomotor can generate 1O2 to achieve PDT and be traced in real time serving as an effective fluorescent bio-radar for intracellular self-reporting during cancer treatment. Finally, the targeting ability of MUHA is provided by hyaluronan. Taken together, this MHUA platform provides a simple and effective strategy for target/fluorescence radar detective-guided PTT/PDT combination, and achieves good therapeutic results without chemodrug under thermal accelerated strategy, providing a new idea for the construction of chemodrug-free nanomotor-therapy system.

Super-Assembled Multilayered Mesoporous TiO2 Nanorockets for Light-Powered Space-Confined Microfluidic Catalysis.

In the field of sustainable chemistry, it is still a significant challenge to realize efficient light-powered space-confined catalysis and propulsion due to the limited solar absorption efficiency and the low mass and heat transfer efficiency. Here, novel semiconductor TiO2 nanorockets with asymmetric, hollow, mesoporous, and double-layer structures are successfully constructed through a facile interfacial superassembly strategy. The high concentration of defects and unique topological features improve light scattering and reduce the distance for charge migration and directed charge separation, resulting in enhanced light harvesting in the confined nanospace and resulting in enhanced catalysis and self-propulsion. The movement velocity of double-layered nanorockets can reach up to 10.5 µm s-1 under visible light, which is approximately 57 and 119% higher than that of asymmetric single-layered TiO2 and isotropic hollow TiO2 nanospheres, respectively. In addition, the double-layered nanorockets improve the degradation rate of the common pollutant methylene blue under sustainable visible light with a 247% rise of first-order rate constant compared to isotropic hollow TiO2 nanospheres. Furthermore, FEA simulations reveal and confirm the double-layered confined-space enhanced catalysis and self-propulsion mechanism.

Biomimetic Self-Propelled Asymmetric Nanomotors for Cascade-Targeted Treatment of Neurological Inflammation.

The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the blood‒brain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.

Strategic Structural Control of Polyserotonin Nanoparticles and Their Application as pH-Responsive Nanomotors.

Serotonin-based nanomaterials have been positioned as promising contenders for constructing multifunctional biomedical nanoplatforms due to notable biocompatibility, advantageous charge properties, and chemical adaptability. The elaborately designed structure and morphology are significant for their applications as functional carriers. In this study, we fabricated anisotropic bowl-like mesoporous polyserotonin (PST) nanoparticles with a diameter of approximately 170 nm through nano-emulsion polymerization, employing P123/F127 as a dual-soft template and 1,3,5-trimethylbenzene (TMB) as both pore expander and emulsion template. Their formation can be attributed to the synchronized assembly of P123/F127/TMB, along with the concurrent manifestation of anisotropic nucleation and growth on the TMB emulsion droplet surface. Meanwhile, the morphology of PST nanoparticles can be regulated from sphere- to bowl-like, with a particle size distribution ranging from 432 nm to 100 nm, experiencing a transformation from a dendritic, cylindrical open mesoporous structure to an approximately non-porous structure by altering the reaction parameters. The well-defined mesopores, intrinsic asymmetry, and pH-dependent charge reversal characteristics enable the as-prepared mesoporous bowl-like PST nanoparticles' potential for constructing responsive biomedical nanomotors through incorporating some catalytic functional materials, 3.5 nm CeO2 nanoenzymes, as a demonstration. The constructed nanomotors demonstrate remarkable autonomous movement capabilities under physiological H2O2 concentrations, even at an extremely low concentration of 0.05 mM, showcasing the 51.58 body length/s velocity. Furthermore, they can also respond to physiological pH values ranging from 4.4 to 7.4, exhibiting reduced mobility with increasing pH. This charge reversal-based responsive nanomotor design utilizing PST nanoparticles holds great promise for advancing the application of nanomotors within complex biological systems.

Carbon monoxide-releasing nanomotors based on endogenous biochemical reactions for tumor therapy.

The lack of selective release ability in the tumor microenvironment and the limited efficacy of monotherapy are important factors that limit the current use of carbon monoxide (CO) donors for tumor therapy. Herein, inspired by endogenous biochemical reactions in vivo, one kind of CO-releasing nanomotor was designed for the multimodal synergistic treatment of tumor. Specifically, glucose oxidase (GOx) and 5-aminolevulinic acid (5-ALA) were co-modified onto metal-organic framework material (MIL-101) to obtain MIL-GOx-ALA nanomotors (M-G-A NMs), which exhibit excellent biocompatibility and degradation ability in tumor microenvironment. Subsequently, the released 5-ALA generates CO in the tumor microenvironment through an endogenous reaction and further acts on mitochondria to release large amounts of reactive oxygen species (ROS), which directly kill tumor cells. Furthermore, the produced ROS and the degradation products of M-G-A NMs can also provide the reaction substrate for the Fenton reaction, thereby enhancing chemodynamic therapy (CDT) and inducing apoptosis of tumor cells. Both in vitro and in vivo experimental data confirm the successful occurrence of the above process, and the combination of CO gas therapy/enhanced CDT can effectively inhibit tumor growth. This CDT-enhancing agent designed based on endogenous biochemical reactions has good prospects for tumor treatment application.

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.

pH-Sensitive Glucose-Powered Nanomotors for Enhanced Intracellular Drug Delivery and Ferroptosis Efficiency.

We propose a glucose-powered Janus nanomotor where two faces are functionalized with glucose oxidase (GOx) and polydopamine-Fe3+ chelates (PDF), respectively. In the glucose fuel solution, the GOx on the one side of these Janus nanomotors catalytically decomposes glucose fuels into gluconic acid and hydrogen peroxide (H2 O2 ) to drive them at a speed of 2.67 µm/s. The underlying propulsion mechanism is the glucose-based self-diffusiophoresis owing to the generated local glucose concentration gradient by the enzymatic reaction. Based on the enhanced diffusion motion, such nanomotors with catalytic activity increase the uptake towards cells and subsequently exhibit excellent capabilities for Fe3+ ions delivery and H2 O2 generation for enhancing ferroptosis efficiency for inducing cancer cell death. In particular, the Fe3+ ions are released from nanomotors in a slightly acidic environment, and subsequently generate toxic hydroxyl radicals via Fenton reactions, which accumulation reactive oxygen species (ROS) level (~300 %) and further lipid peroxidation (LPO) strengthened ferroptosis therapy for cancer treatment. The as-developed glucose-powered Janus nanomotor with efficient diffusion and Fe ions delivery capabilities show great promise as a potential in biomedical applications.

Targeting Nanomotor with Near-Infrared/Ultrasound Triggered-Transformation for Polystage-Propelled Cascade Thrombolysis and Multimodal Imaging Diagnosis.

Nowadays, cardiovascular and cerebrovascular diseases caused by venous thromboembolism become main causes of mortality around the world. The current thrombolytic strategies in clinics are confined primarily due to poor penetration of nanoplatforms, limited thrombolytic efficiency, and extremely-low imaging accuracy. Herein, a novel nanomotor (NM) is engineered by combining iron oxide/perfluorohexane (PFH)/urokinase (UK) into liposome nanovesicle, which exhibits near-infrared/ultrasound (NIR/US) triggered transformation, achieves non-invasive vein thrombolysis, and realizes multimodal imaging diagnosis altogether. Interestingly, a three-step propelled cascade thrombolytic therapy is revealed from such intelligent NM. First, the NM is effectively herded at the thrombus site under guidance of a magnetic field. Afterwards, stimulations of NIR/US propel phase transition of PFH, which intensifies penetration of the NM toward deep thrombus dependent on cavitation effect. Ultimately, UK is released from the collapsed NM and achieves pharmaceutical thrombolysis in a synergistic way. After an intravenous injection of NM in vivo, the whole thrombolytic process is monitored in real-time through multimodal photoacoustic, ultrasonic, and color Doppler ultrasonic imagings. Overall, such advanced nanoplatform provides a brand-new strategy for time-critical vein thrombolytic therapy through efficient thrombolysis and multimodal imaging diagnosis.