Bacterial outer membrane vesicle nanorobot.

Autonomous nanorobots represent an advanced tool for precision therapy to improve therapeutic efficacy. However, current nanorobotic designs primarily rely on inorganic materials with compromised biocompatibility and limited biological functions. Here, we introduce enzyme-powered bacterial outer membrane vesicle (OMV) nanorobots. The immobilized urease on the OMV membrane catalyzes the decomposition of bioavailable urea, generating effective propulsion for nanorobots. This OMV nanorobot preserves the unique features of OMVs, including intrinsic biocompatibility, immunogenicity, versatile surface bioengineering for desired biofunctionalities, capability of cargo loading and protection. We present OMV-based nanorobots designed for effective tumor therapy by leveraging the membrane properties of OMVs. These involve surface bioengineering of robotic body with cell-penetrating peptide for tumor targeting and penetration, which is further enhanced by active propulsion of nanorobots. Additionally, OMV nanorobots can effectively safeguard the loaded gene silencing tool, small interfering RNA (siRNA), from enzymatic degradation. Through systematic in vitro and in vivo studies using a rodent model, we demonstrate that these OMV nanorobots substantially enhanced siRNA delivery and immune stimulation, resulting in the utmost effectiveness in tumor suppression when juxtaposed with static groups, particularly evident in the orthotopic bladder tumor model. This OMV nanorobot opens an inspiring avenue to design advanced medical robots with expanded versatility and adaptability, broadening their operation scope in practical biomedical domains.

Autonomous Nanorobots as Miniaturized Surgeons for Intracellular Applications.

Artificial nanorobots have emerged as promising tools for a wide range of biomedical applications, including biosensing, detoxification, and drug delivery. Their unique ability to navigate confined spaces with precise control extends their operational scope to the cellular or subcellular level. By combining tailored surface functionality and propulsion mechanisms, nanorobots demonstrate rapid penetration of cell membranes and efficient internalization, enhancing intracellular delivery capabilities. Moreover, their robust motion within cells enables targeted interactions with intracellular components, such as proteins, molecules, and organelles, leading to superior performance in intracellular biosensing and organelle-targeted cargo delivery. Consequently, nanorobots hold significant potential as miniaturized surgeons capable of directly modulating cellular dynamics and combating metastasis, thereby maximizing therapeutic outcomes for precision therapy. In this review, we provide an overview of the propulsion modes of nanorobots and discuss essential factors to harness propulsive energy from the local environment or external power sources, including structure, material, and engine selection. We then discuss key advancements in nanorobot technology for various intracellular applications. Finally, we address important considerations for future nanorobot design to facilitate their translation into clinical practice and unlock their full potential in biomedical research and healthcare.

Magnetically Powered Immunogenic Macrophage Microrobots for Targeted Multimodal Cancer Therapy.

Motile microrobots open a new realm for disease treatment. However, the concerns of possible immune elimination, targeted capability and limited therapeutic avenue of microrobots constrain its practical biomedical applications. Herein, a biogenic macrophage-based microrobot loaded with magnetic nanoparticles and bioengineered bacterial outer membrane vesicles (OMVs), capable of magnetic propulsion, tumor targeting, and multimodal cancer therapy is reported. Such cell robots preserve intrinsic properties of macrophages for tumor suppression and targeting, and bioengineered OMVs for antitumor immune regulation and fused anticancer peptides. Cell robots display efficient magnetic propulsion and directional migration in the confined space. In vivo tests show that cell robots can accumulate at the tumor site upon magnetic manipulation, coupling with tumor tropism of macrophages to greatly improve the efficacy of its multimodal therapy, including tumor inhibition of macrophages, immune stimulation, and antitumor peptides of OMVs. This technology offers an attractive avenue to design intelligent medical microrobots with remote manipulation and multifunctional therapy capabilities for practical precision treatment.

Autonomous metal-organic framework nanorobots for active mitochondria-targeted cancer therapy.

Nanorobotic manipulation to access subcellular organelles remains unmet due to the challenge in achieving intracellular controlled propulsion. Intracellular organelles, such as mitochondria, are an emerging therapeutic target with selective targeting and curative efficacy. We report an autonomous nanorobot capable of active mitochondria-targeted drug delivery, prepared by facilely encapsulating mitochondriotropic doxorubicin-triphenylphosphonium (DOX-TPP) inside zeolitic imidazolate framework-67 (ZIF-67) nanoparticles. The catalytic ZIF-67 body can decompose bioavailable hydrogen peroxide overexpressed inside tumor cells to generate effective intracellular mitochondriotropic movement in the presence of TPP cation. This nanorobot-enhanced targeted drug delivery induces mitochondria-mediated apoptosis and mitochondrial dysregulation to improve the in vitro anticancer effect and suppression of cancer cell metastasis, further verified by in vivo evaluations in the subcutaneous tumor model and orthotopic breast tumor model. This nanorobot unlocks a fresh field of nanorobot operation with intracellular organelle access, thereby introducing the next generation of robotic medical devices with organelle-level resolution for precision therapy.

Pollen Typhae-Based Magnetic-Powered Microrobots toward Acute Gastric Bleeding Treatment.

Traditional Chinese herbal medicine (TCHM) is the naturally available pharmaceutical with millennia of evolution from ancient China, capable of a superior therapeutic index and minimized unwanted effects on the human body. This work presents a therapeutic microrobotic platform based on pollen typhae (PT), a typical type of TCHM, fabricated by coating porous PT microspheres with Fe3O4 nanoparticles (PT robots) via electrostatic adsorption. The PT robots exhibit effective and controllable motion in various biological media upon external magnetic control and, meanwhile, preserve the inherent hemostasis property of PT. The blood clotting capacity of PT robots is attributed to their stimulation of the endogenous blood coagulation pathway and platelets with increased counts, which could be further improved by their effective magnetic propulsion. The remote magnetic control also allows the manipulation of PT robots in mice stomach, inducing enhanced binding and prolonged retention of PT robots in stomach mucosa. Moreover, PT robots upon magnetic control show an enhanced hemostatic effect in treating the mice bearing acute gastric bleeding compared with other passive groups. This work offers a facile and feasible route to integrate TCHM with manmade micromachines possessing the innate curative features of TCHM. Such a design expanded the versatility of microrobots and can be generalized to vast types of TCHM for broader biomedical applications.

Centrifugal Spinning Enables the Formation of Silver Microfibers with Nanostructures.

Silver nanowires (AgNWs) have received much attention and application in transparent electrodes, wearable electronic devices, and sensors. The hope is for these nanowires to eventually replace the most commonly used transparent electrode material-indium tin oxide (ITO). However, electrospinning used for the preparation of AgNWs on a large scale is limited by its low productivity and high electric field, while the alcohol-thermal method is limited to mixing by-product silver nanoparticles in silver nanowires. We demonstrate a novel and simple centrifugal spinning approach in order to successfully fabricate ultra-long silver microfibers based on AgNO3 and polyvinyl pyrrolidone (PVP). The centrifugal-spun precursor fiber and silver fiber can be prepared to as thin as 390 and 310 nm, respectively. Annealed fibers show typical nanostructures with grains down to a minimum size of 51 nm. Combinations of different parameters, including concentrations of PVP, needle size, and annealing temperature are also investigated, in order to optimize the spinning process of ultra-long silver microfibers. The feasibility of preparing silver microfibers by centrifugal spinning is preliminarily verified, examining prospects for mass production. Furthermore, numerous strategies related to assisting the creation of silver nanofibers using centrifugal spinning are presented as possibilities in future development.

Magnetic-Powered Janus Cell Robots Loaded with Oncolytic Adenovirus for Active and Targeted Virotherapy of Bladder Cancer.

A unique robotic medical platform is designed by utilizing cell robots as the active "Trojan horse" of oncolytic adenovirus (OA), capable of tumor-selective binding and killing. The OA-loaded cell robots are fabricated by entirely modifying OA-infected 293T cells with cyclic arginine-glycine-aspartic acid tripeptide (cRGD) to specifically bind with bladder cancer cells, followed by asymmetric immobilization of Fe3 O4 nanoparticles (NPs) on the cell surface. OA can replicate in host cells and induce cytolysis to release the virus progeny to the surrounding tumor sites for sustainable infection and oncolysis. The asymmetric coating of magnetic NPs bestows the cell robots with effective movement in various media and wireless manipulation with directional migration in a microfluidic device and bladder mold under magnetic control, further enabling steerable movement and prolonged retention of cell robots in the mouse bladder. The biorecognition of cRGD and robust, controllable propulsion of cell robots work synergistically to greatly enhance their tissue penetration and anticancer efficacy in the 3D cancer spheroid and orthotopic mouse bladder tumor model. Overall, this study integrates cell-based microrobots with virotherapy to generate an attractive robotic system with tumor specificity, expanding the operation scope of cell robots in biomedical community.

Artificial photoactive chlorophyll conjugated vanadium carbide nanostructure for synergistic photothermal/photodynamic therapy of cancer.

Optically active nanostructures consisting of organic compounds and metallic support have shown great promise in phototherapy due to their increased light absorption capacity and high energy conversion. Herein, we conjugated chlorophyll (Chl) to vanadium carbide (V2C) nanosheets for combined photodynamic/photothermal therapy (PDT/PTT), which reserves the advantages of each modality while minimizing the side effects to achieve an improved therapeutic effect. In this system, the Chl from Leptolyngbya JSC-1 extracts acted as an efficient light-harvest antenna in a wide NIR range and photosensitizers (PSs) for oxygen self-generation hypoxia-relief PDT. The available large surface of two-dimensional (2D) V2C showed high Chl loading efficiency, and the interaction between organic Chl and metallic V2C led to energy conversion efficiency high to 78%. Thus, the Chl/ V2C nanostructure showed advanced performance in vitro cell line killing and completely ablated tumors in vivo with 100% survival rate under a single NIR irradiation. Our results suggest that the artificial optical Chl/V2C nanostructure will benefit photocatalytic tumor eradication clinic application.

Robust multifunctional superhydrophobic, photocatalytic and conductive fabrics with electro-/photo-thermal self-healing ability.

The fabrication of superhydrophobic and conductive fabrics that can conveniently and repeatedly restore the lost superhydrophobicity, caused by either the surface accumulation of trace organic contaminants or the chemical damage to surface components, remains challenging. Herein, we report a multifunctional superhydrophobic and conductive cotton fabric that integrates not only the photocatalytic activity for cleaning organic contaminants, but also the self-healing ability enabled by either electro-thermal or photo-thermal heating besides convection oven heating. The fabric was fabricated through the polydopamine (PDA)-assisted deposition of photocatalyst Ag/CdS and the subsequent thiol-Ag self-assembly. Either UV or visible light irradiation is able to decompose the surface organic contaminants, and the photocatalysis-induced slight damage on super water-repellency is curable by heating. The Ag layer endows the fabric with antibacterial property and conductivity along with the electro-/photo-thermal conversion ability, which offers relatively convenient ways of heating for curing the surface chemical damages caused by O2 plasma etching or accelerated washing. Of particular importance is that the fabric still shows super water-repellency even after 18 cycles of accelerated washing, which equals to 90 normal home laundering cycles. The combination of these multiple functions makes this fabric very promising for a wide range of wearable applications.

Multiple amplified microRNAs monitoring in living cells based on fluorescence quenching of Mo2B and hybridization chain reaction.

Imaging intracellular microRNAs (miRNAs) demonstrated an essential role in exposing their biological and pathological functions. However, the detection of sequence-specific miRNAs in living cells remains a key challenge. Herein, a facile amplified multiple intracellular miRNAs imaging platform was constructed based on Mo2B nanosheets (NSs) fluorescence (FL) quenching and hybridization chain reaction (HCR). The Mo2B NSs demonstrated strong interaction with the hairpin probes (HPs), ssDNA loop, and excellent multiple FL dyes quenching performance, achieving ultralow background signal. After transfection, the HPs recognized specific targets miRNAs, the corresponding HCR was triggered to produce tremendous DNA-miRNA duplex helixes, which dissociated from the surface of the Mo2B NSs to produce strong FL for miRNAs detection. It realized to image multiple miRNAs biomarkers in different cells to discriminate cancer cells from normal cells owing to the excellent sensitivity, and the regulated expression change of miRNAs in cancer cells was also successfully monitored. The facile and versatile Mo2B-based FL quenching platform open an avenue to profile miRNAs expression pattern in living cells, and has great applications in miRNAs based biological and biomedical research.

Multifunctional Metal-Organic Framework Exoskeletons Protect Biohybrid Sperm Microrobots for Active Drug Delivery from the Surrounding Threats.

Utilizing spermatozoa as the engine unit of robotic systems at a microscale has brought revolutionized inspirations and strategies to the biomedical community. However, the motility of sperms is impaired by the surrounding threats. For example, the antisperm antibody (AsA) can specifically bind with surface antigens on the sperm membrane and adversely affect their propulsion, hindering the operation of sperm-based microrobots in practical environments. In the present work, we report a biohybrid sperm microrobot by encapsulating sperm cells within metal-organic frameworks (MOFs) and zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) (ZIFSpermbot), capable of active drug delivery and cytoprotection from the biological threats of AsA. ZIF-8 NPs can be facilely coated on the sperm membrane through complexation with tannic acid. Such cell surface engineering has a negligible impact on sperm motility under optimized conditions. The selective permeability of the resulting porous ZIF-8 wrappings protects ZIFSpermbots from the specific binding of AsA, enabling the preservation of intrinsic propulsion of the sperm engine. Besides, ZIF-8 wrappings sustainably release zinc ions and attenuate the oxidative damage generated in sperm cells, allowing the maintenance of sperm movement. Combining the effective protection of sperm propulsion with the drug-loading capacity of ZIF-8 NPs provides new applicability to ZIFSpermbots in risky surroundings with AsA, exhibiting rapid migration in a microfluidic device for active drug delivery with enhanced therapeutic efficacy due to their retained effective propulsion. Imparting bioengine-based microrobots with multifunctional wrappings holds great promise for designing adaptive cell robots that endure harsh environments toward locally extended and diverse operations, facilitating their use in practical and clinical applications.

Quantitative accuracy in total-body imaging using the uEXPLORER PET/CT scanner.

Absolute quantification of regional tissue concentration of radioactivity in positron emission tomography (PET) is a critical parameter-of-interest across various clinical and research applications and is affected by a complex interplay of factors including scanner calibration, data corrections, and image reconstruction. The emergence of long axial field-of-view (FOV) PET systems widens the dynamic range accessible to PET and creates new opportunities in reducing scan time and radiation dose, delayed or low radioactivity imaging, as well as kinetic modeling of the entire human. However, these imaging regimes impose challenging conditions for accurate quantification due to constraints from image reconstruction, low count conditions, as well as large and rapidly changing radioactivity distribution across a large axial FOV. We comprehensively evaluated the quantitative accuracy of the uEXPLORER total-body scanner in conditions that encompass existing and potential imaging applications (such as dynamic imaging and ultralow-dose imaging) using a set of total-body specific phantom and human measurements. Through these evaluations we demonstrated a relative count rate accuracy of ±3%-4% using the NEMA NU 2-2018 protocol, an axial uniformity spread of ±3% across the central 90% axial FOV, and a 3% activity bias spread from 17 to 474 MBq18F-FDG in a 210 cm long cylindrical phantom. Region-of-interest quantification spread of 1% was found by simultaneously scanning three NEMA NU 2 image quality phantoms, as well as relatively stable volume-of-interest quantification across 0.2%-100% of total counts through re-sampled datasets. In addition, an activity bias spread of -2% to +1% post-bolus injections in human subjects was found. Larger bias changes during the bolus injection phase in humans indicated the difficulty in providing accurate PET data corrections for complex activity distributions across a large dynamic range. Our results overall indicated that the quantitative performance achieved with the uEXPLORER scanner was uniform across the axial FOV and provided the accuracy necessary to support a wide range of imaging applications.

Magnetic-Propelled Janus Yeast Cell Robots Functionalized with Metal-Organic Frameworks for Mycotoxin Decontamination.

Cell robots that transform natural cells into active platforms hold great potential to enrich the biomedical prospects of artificial microrobots. Here, we present Janus yeast cell microrobots (JYC-robots) prepared by asymmetrically coating Fe3O4 nanoparticles (NPs) and subsequent in situ growth of zeolitic imidazolate framework-67 (ZIF-67) on the surface of yeast cells. The magnetic actuation relies on the Fe3O4 NPs wrapping. As the compositions of cell robots, the cell wall with abundant polysaccharide coupling with porous and oxidative ZIF-67 can concurrently remove mycotoxin (e.g., zearalenone (ZEN)). The magnetic propulsion accelerates the decontamination efficiency of JYC-robots against ZEN. Although yeast cells with fully coating of Fe3O4 NPs and ZIF-67 (FC-yeasts) show faster movement than JYC-robots, higher toxin-removal efficacy is observed for JYC-robots compared with that of FC-yeasts, reflecting the vital factor of the yeast cell wall in removing mycotoxin. Such design with Janus modification of magnetic NPs (MNPs) and entire coating of ZIF-67 generates active cell robot platform capable of fuel-free propulsion and enhanced detoxification, offering a new formation to develop cell-based robotics system for environmental remediation.

Durable superhydrophobic cotton fabrics prepared by surface-initiated electrochemically mediated ATRP of polyhedral vinylsilsesquioxane and subsequent fluorination via thiol-Michael addition reaction.

Fluorinated polyhedral oligomeric silsesquioxane (F-POSS) is one of the most popular candidates at present for superhydrophobic coating. Because of its ultralow surface energy, F-POSS has usually been dissolved with expensive fluoro-solvents, and the melting temperature of F-POSS is not high (122-140 °C), which will cause its loss during use. So trying to polymerize/crosslink F-POSS molecules and/or directly graft F-POSS to substrate is important. In this work, we report the SI-eATRP grafting of methacryl POSS (MA-POSS) on cotton and the subsequent amine catalyzed thiol-methacrylate Michael addition reaction of poly(MA-POSS) with 1H, 1H, 2H, 2H-perfluorododecyl-1-thiol (PFDT) for the fabrication of a durable poly(MA-POSS)-PFDT coating. The cotton fabric coated with poly(MA-POSS) was nearly superhydrophobic after 4 h of SI-eATRP process under potentiostatic condition of -0.40 V. Although the water contact angle (WCA) was ~148°, water droplets tended to adhere to the cotton fabric surface even when the fabric was turned upside down. After fluorination, WCA was increased to ~160°, and water drops could slide off when the fabric was slightly tilted. The sliding angle (SA) was ~10°. The as-prepared poly(MA-POSS)-PFDT coating was durable against repeated washing and physical abrasion. After 30 accelerated washing cycles (equals to 150 home laundering cycles), the coated fabric still showed superhydrophobicity. After 800 abrasion cycles over sandpaper, the WCA was still as high as 149°. In addition, the coated fabric had self-healing ability and could restore its superhydrophobicity after plasma etching through heat treatment. After 10 cycles of plasma etching and heat-induced healing process, the WCA of the coated fabric kept at ~154°. Such a durable superhydrophobic fabric coating may find applications in the development of functional clothing for a variety of purposes.

V2C Nanosheets as Dual-Functional Antibacterial Agents.

Antibiotic-resistant bacterial strains have been continuously increasing and becoming a supreme threat to public health globally. The nanoparticle-based photothermal treatment has emerged as a powerful tool to combat toxic bacteria. Photothermal agents (PTAs) with cost-effective and high photothermal conversion efficiency are highly desirable. Herein, we unite the green process for delamination of V2AlC to produce a high yield mass of two-dimensional (2D) V2C nanosheets (NSs) by using algae extracts and demonstrate their high antibacterial efficiency. The resultant V2C NSs present decent structural reliability and intrinsic antibacterial ability. Powerful near-infrared (NIR) absorption and extraordinary photothermal conversion proficiency make it a good PTA for the photothermal treatment of bacteria. The antibacterial efficiency evaluation indicated that V2C NSs could effectively kill both Gram-positive S. aureus and Gram-negative E. coli. About 99.5% of both types of bacteria could be killed with low-dose of V2C NSs suspension (40 µg/mL) with 5 min NIR irradiation due to the intrinsic antibacterial ability and photothermal effect of V2C NSs, which is much higher than previous reports on Ta4C3, Ti3C2, MoSe2, and Nb2C. This work expands the application of MXene V2C NSs for rapid bacteria-killing and would gain promising attention for applications in the sterilization industry.

Performance Evaluation of the uEXPLORER Total-Body PET/CT Scanner Based on NEMA NU 2-2018 with Additional Tests to Characterize PET Scanners with a Long Axial Field of View.

The world's first total-body PET scanner with an axial field of view (AFOV) of 194 cm is now in clinical and research use at our institution. The uEXPLORER PET/CT system is the first commercially available total-body PET scanner. Here we present a detailed physical characterization of this scanner based on National Electrical Manufacturers Association (NEMA) NU 2-2018 along with a new set of measurements devised to appropriately characterize the total-body AFOV. Methods: Sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, and image quality were evaluated following the NEMA NU 2-2018 protocol. Additional measurements of sensitivity and count-rate capabilities more representative of total-body imaging were performed using extended-geometry phantoms based on the world-average human height (∼165 cm). Lastly, image quality throughout the long AFOV was assessed with the NEMA image quality (IQ) phantom imaged at 5 axial positions and over a range of expected total-body PET imaging conditions (low dose, delayed imaging, short scan duration). Results: Our performance evaluation demonstrated that the scanner provides a very high sensitivity of 174 kcps/MBq, a count-rate performance with a peak noise-equivalent count rate of approximately 2 Mcps for total-body imaging, and good spatial resolution capabilities for human imaging (≤3.0 mm in full width at half maximum near the center of the AFOV). Excellent IQ, excellent contrast recovery, and low noise properties were illustrated across the AFOV in both NEMA IQ phantom evaluations and human imaging examples. Conclusion: In addition to standard NEMA NU 2-2018 characterization, a new set of measurements based on extending NEMA NU 2-2018 phantoms and experiments was devised to characterize the physical performance of the first total-body PET system. The rationale for these extended measurements was evident from differences in sensitivity, count-rate-activity relationships, and noise-equivalent count-rate limits imposed by differences in dead time and randoms fraction between the NEMA NU 2 70-cm phantoms and the more representative total-body imaging phantoms. Overall, the uEXPLORER PET system provides ultra-high sensitivity that supports excellent spatial resolution and IQ throughout the field of view in both phantom and human imaging.

Enzyme-powered Janus platelet cell robots for active and targeted drug delivery.

Transforming natural cells into functional biocompatible robots capable of active movement is expected to enhance the functions of the cells and revolutionize the development of synthetic micromotors. However, present cell-based micromotor systems commonly require the propulsion capabilities of rigid motors, external fields, or harsh conditions, which may compromise biocompatibility and require complex actuation equipment. Here, we report on an endogenous enzyme-powered Janus platelet micromotor (JPL-motor) system prepared by immobilizing urease asymmetrically onto the surface of natural platelet cells. This Janus distribution of urease on platelet cells enables uneven decomposition of urea in biofluids to generate enhanced chemophoretic motion. The cell surface engineering with urease has negligible impact on the functional surface proteins of platelets, and hence, the resulting JPL-motors preserve the intrinsic biofunctionalities of platelets, including effective targeting of cancer cells and bacteria. The efficient propulsion of JPL-motors in the presence of the urea fuel greatly enhances their binding efficiency with these biological targets and improves their therapeutic efficacy when loaded with model anticancer or antibiotic drugs. Overall, asymmetric enzyme immobilization on the platelet surface leads to a biogenic microrobotic system capable of autonomous movement using biological fuel. The ability to impart self-propulsion onto biological cells, such as platelets, and to load these cellular robots with a variety of functional components holds considerable promise for developing multifunctional cell-based micromotors for a variety of biomedical applications.

Core@Satellite Janus Nanomotors with pH-Responsive Multi-phoretic Propulsion.

We report core@satellite Janus mesoporous silica-Pt@Au (JMPA) nanomotors with pH-responsive multi-phoretic propulsion. The JMPA nanomotors first undergo self-diffusiophoretic propulsion in 3.0 % H2 O2 due to the isolation of the Au nanoparticles (AuNPs) from the PtNPs layer. Then the weak acidity of H2 O2 can trigger the disassembly and reassembly of the AuNPs, resulting in the Janus distribution of large AuNPs aggregates. Such reconstruction of JMPA leads to the contact between PtNPs and AuNPs aggregates, thus changing the propulsion mechanism to self-electrophoresis. The asymmetric and aggregated AuNPs also enable the generation of a thermal gradient under laser irradiation, which propels the JMPA nanomotors by self-thermophoresis. Such multi-phoretic propulsion offers considerable promise for developing advanced nanomachines with a stimuli-responsive switch of propulsion modes in biomedical applications.