Electrochemical Activation Inducing Rocksalt-to-Spinel Transformation for Prolonged Service Life of LiMn2O4 Cathodes.

LiMn2O4 spinel is emerging as a promising cathode material for lithium-ion batteries, largely due to its open framework that facilitates Li+ diffusion and excellent rate performance. However, the charge-discharge cycling of the LiMn2O4 cathode leads to severe structural degradation and rapid capacity decay. Here, an electrochemical activation strategy is introduced, employing a facile galvano-potentiostatic charging operation, to restore the lost capacity of LiMn2O4 cathode without damaging the battery configuration. With an electrochemical activation strategy, the cycle life of the LiMn2O4 cathode is extended from an initial 1500 to an impressive 14 000 cycles at a 5C rate with Li metal as the anode, while increasing the total discharge energy by ten times. Remarkably, the electrochemical activation enhances the diffusion kinetics of Li+, with the diffusion coefficient experiencing a 37.2% increase. Further investigation reveals that this improvement in capacity and diffusion kinetics results from a transformation of the redox-inert LiMnO2 rocksalt layer on the surface of degraded cathodes back into active spinel. This transformation is confirmed through electron microscopy and corroborated by density functional theory simulations. Moreover, the viability of this electrochemical activation strategy has been demonstrated in pouch cell configurations with Li metal as the anode, underscoring its potential for broader application.

Microelectrochemical Sensor Reveals Tunneling Nanotube-Mediated Intercellular Communication of Endothelial Mechanotransduction.

The intercellular communication of mechanotransduction has a significant impact on various cellular processes. Tunneling nanotubes (TNTs) have been documented to possess the capability of transmitting mechanical stimulation between cells, thereby triggering an influx of Ca2+ ions. However, the related kinetic information on the TNT-mediated intercellular mechanotransduction communication is still poorly explored. Herein, we developed a classic and sensitive Pt-functionalized carbon fiber microelectrochemical sensor (Pt/CF) to study the intercellular communication of endothelial mechanotransduction through TNTs. The experimental findings demonstrate that the transmission of mechanical stimulation from stimulated human umbilical vein endothelial cells (HUVECs) to recipient HUVECs connected by TNTs occurred quickly (<100 ms) and effectively promoted nitric oxide (NO) production in the recipient HUVECs. The kinetic profile of NO release exhibited remarkable similarity in stimulated and recipient HUVECs. But the production of NO in the recipient cell is significantly attenuated (16.3%) compared to that in the stimulated cell, indicating a transfer efficiency of approximately 16.3% for TNTs. This study unveils insights into the TNT-mediated intercellular communication of mechanotransduction.

A Highly Selective Implantable Electrochemical Fiber Sensor for Real-Time Monitoring of Blood Homovanillic Acid.

Homovanillic acid (HVA) is a major dopamine metabolite, and blood HVA is considered as central nervous system (CNS) dopamine biomarker, which reflects the progression of dopamine-associated CNS diseases and the behavioral response to therapeutic drugs. However, facing blood various active substances interference, particularly structurally similar catecholamines and their metabolites, real-time and accurate monitoring of blood HVA remains a challenge. Herein, a highly selective implantable electrochemical fiber sensor based on a molecularly imprinted polymer is reported to accurately monitor HVA in vivo. The sensor exhibits high selectivity, with a response intensity to HVA 12.6 times greater than that of catecholamines and their metabolites, achieving 97.8% accuracy in vivo. The sensor injected into the rat caudal vein tracked the real-time changes of blood HVA, which paralleled the brain dopamine fluctuations and indicated the behavioral response to dopamine increase. This study provides a universal design strategy for improving the selectivity of implantable electrochemical sensors.

Interface-Stabilized Fiber Sensor for Real-Time Monitoring of Amniotic Fluid During Pregnancy.

Diseases in pregnancy endanger millions of fetuses worldwide every year. The onset of these diseases can be early warned by the dynamic abnormalities of biochemicals in amniotic fluid, thus requiring real-time monitoring. However, when continuously penetrated by detection devices, the amnion is prone to loss of robustness and rupture, which is difficult to regenerate. Here, an interface-stabilized fiber sensor is presented for real-time monitoring of biochemical dynamics in amniotic fluid during pregnancy. The sensor is seamlessly integrated into the amnion through tissue adhesion, amniotic regeneration, and uniform stress distribution, posing no risk to the amniotic fluid environment. The sensor demonstrates a response performance of less than 0.3% fluctuation under complex dynamic conditions and an accuracy of more than 98% from the second to the third trimester. By applying it to early warning of diseases such as intrauterine hypoxia, intrauterine infection, and fetal growth restriction, fetal survival increases to 95% with timely intervention.

Graph Evolution-Based Vertex Extraction for Hyperspectral Anomaly Detection.

Anomaly detection is a fundamental task in hyperspectral image (HSI) processing. However, most existing methods rely on pixel feature vectors and overlook the relational structure information between pixels, limiting the detection performance. In this article, we propose a novel approach to hyperspectral anomaly detection that characterizes the HSI data using a vertex-and edge-weighted graph with the pixels as vertices. The constructed graph encodes rich structural information in an affinity matrix. A crucial innovation of our method is the ability to obtain internal relations between pixels at multiple topological scales by processing different powers of the affinity matrix. This power processing is viewed as a graph evolution, which enables anomaly detection using vertex extraction formulated as a quadratic programming problem on graphs of varying topological scales. We also design a hierarchical guided filtering architecture to fuse multiscale detection results derived from graph evolution, which significantly reduces the false alarm rate. Our approach effectively characterizes the topological properties of HSIs, leveraging the structural information between pixels to improve anomaly detection accuracy. Experimental results on four real HSIs demonstrate the superior detection performance of our proposed approach compared to some state-of-the-art hyperspectral anomaly detection methods.

Biofilm Microenvironment-Responsive Self-Assembly Nanoreactors for All-Stage Biofilm Associated Infection through Bacterial Cuproptosis-like Death and Macrophage Re-Rousing.

Bacterial biofilm-associated infections (BAIs) are the leading cause of prosthetic implant failure. The dense biofilm structure prevents antibiotic penetration, while the highly acidic and H2 O2 -rich biofilm microenvironment (BME) dampens the immunological response of antimicrobial macrophages. Conventional treatments that fail to consistently suppress escaping planktonic bacteria from biofilm result in refractory recolonization, allowing BAIs to persist. Herein, a BME-responsive copper-doped polyoxometalate clusters (Cu-POM) combination with mild photothermal therapy (PTT) and macrophage immune re-rousing for BAI eradication at all stages is proposed. The self-assembly of Cu-POM in BME converts endogenous H2 O2 to toxic ·OH through chemodynamic therapy (CDT) and generates a mild PTT effect to induce bacterial metabolic exuberance, resulting in loosening the membrane structure of the bacteria, enhancing copper transporter activity and increasing intracellular Cu-POM flux. Metabolomics reveals that intracellular Cu-POM overload restricts the TCA cycle and peroxide accumulation, promoting bacterial cuproptosis-like death. CDT re-rousing macrophages scavenge planktonic bacteria escaping biofilm disintegration through enhanced chemotaxis and phagocytosis. Overall, BME-responsive Cu-POM promotes bacterial cuproptosis-like death via metabolic interference, while also re-rousing macrophage immune response for further planktonic bacteria elimination, resulting in all-stage BAI clearance and providing a new reference for future clinical application.

Implantable Zinc-Oxygen Battery for In Situ Electrical Stimulation-Promoted Neural Regeneration.

Electrical stimulation is a promising strategy for treating neural diseases. However, current energy suppliers cannot provide effective power for in situ electrical stimulation. Here, an implantable tubular zinc-oxygen battery is reported as the power source for in situ electrical stimulation during the neural repair. The battery exhibited a high volumetric energy density of 231.4 mWh cm-3 based on the entire anode and cathode in vivo. Due to its superior electrochemical properties and biosafety, the battery can be directly wrapped around the nerve to provide in situ electrical stimulation with a minimal size of 0.86 mm3 . The cell and animal experiments demonstrated that the zinc-oxygen battery-based nerve tissue engineering conduit effectively promoted regeneration of the injured long-segment sciatic nerve, proving its promising applications for powering implantable neural electronics in the future.

Biofilm Homeostasis Interference Therapy via 1 O2 -Sensitized Hyperthermia and Immune Microenvironment Re-Rousing for Biofilm-Associated Infections Elimination.

The recurrence of biofilm-associated infections (BAIs) remains high after implant-associated surgery. Biofilms on the implant surface reportedly shelter bacteria from antibiotics and evade innate immune defenses. Moreover, little is currently known about eliminating residual bacteria that can induce biofilm reinfection. Herein, novel "interference-regulation strategy" based on bovine serum albumin-iridium oxide nanoparticles (BIONPs) as biofilm homeostasis interrupter and immunomodulator via singlet oxygen (1 O2 )-sensitized mild hyperthermia for combating BAIs is reported. The catalase-like BIONPs convert abundant H2 O2 inside the biofilm-microenvironment (BME) to sufficient oxygen gas (O2 ), which can efficiently enhance the generation of 1 O2 under near-infrared irradiation. The 1 O2 -induced biofilm homeostasis disturbance (e.g., sigB, groEL, agr-A, icaD, eDNA) can disrupt the sophisticated defense system of biofilm, further enhancing the sensitivity of biofilms to mild hyperthermia. Moreover, the mild hyperthermia-induced bacterial membrane disintegration results in protein leakage and 1 O2 penetration to kill bacteria inside the biofilm. Subsequently, BIONPs-induced immunosuppressive microenvironment re-rousing successfully re-polarizes macrophages to pro-inflammatory M1 phenotype in vivo to devour residual biofilm and prevent biofilm reconstruction. Collectively, this 1 O2 -sensitized mild hyperthermia can yield great refractory BAIs treatment via biofilm homeostasis interference, mild-hyperthermia, and immunotherapy, providing a novel and effective anti-biofilm strategy.

Enzymatic bionanocatalysts for combating peri-implant biofilm infections by specific heat-amplified chemodynamic therapy and innate immunomodulation.

Bacterial biofilm-associated infection is a life-threatening emergency contributing from drug resistance and immune escape. Herein, a novel non-antibiotic strategy based on the synergy of bionanocatalysts-driven heat-amplified chemodynamic therapy (CDT) and innate immunomodulation is proposed for specific biofilm elimination by the smart design of a biofilm microenvironment (BME)-responsive double-layered metal-organic framework (MOF) bionanocatalysts (MACG) composed of MIL-100 and CuBTC. Once reaching the acidic BME, the acidity-triggered degradation of CuBTC allows the sequential release of glucose oxidase (GOx) and an activable photothermal agent, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). GOx converts glucose into H2O2 and gluconic acid, which can further acidify the BME to accelerate the CuBTC degradation and GOx/ABTS release. The in vitro and in vivo results show that horseradish peroxidase (HRP)-mimicking MIL-100 in the presence of self-supplied H2O2 can catalyze the oxidation of ABTS into oxABTS to yield a photothermal effect that breaks the biofilm structure via eDNA damage. Simultaneously, the Cu ion released from the degraded CuBTC can deplete glutathione and catalyze the splitting of H2O2 into •OH, which can effectively penetrate the heat-induced loose biofilms and kill sessile bacteria (up to 98.64%), such as E. coli and MRSA. Particularly, MACG-stimulated M1-macrophage polarization suppresses the biofilm regeneration by secreting pro-inflammatory cytokines (e.g., IL-6, TNF-α, etc.) and forming a continuous pro-inflammatory microenvironment in peri-implant biofilm infection animals for at least 14 days. Such BME-responsive strategy has the promise to precisely eliminate refractory peri-implant biofilm infections with extremely few adverse effects.

Superhydrophobic conductive rubber band with synergistic dual conductive layer for wide-range sensitive strain sensor.

Wearable electronic devices have received increasing interests because of their excellent flexibility, stretchability, and human friendliness. As the core components, flexible strain sensors integrated with wide working range, high sensitivity, and environment stability, especially in moisture or corrosive environments, remain a huge challenge. Herein, synergistic carbon nanotubes (CNTs)/reduced graphene oxide (rGO) dual conductive layer decorated elastic rubber band (RB) was successfully developed and treated with hydrophobic fumed silica (Hf-SiO2) for preparing superhydrophobic strain sensor. As expected, stable entangled CNTs layer and ultrasensitive microcracked rGO layer endow the sensor with extremely low detection limit (0.1%), high sensitivity (gauge factor is 685.3 at 482% strain), wide workable strain range (0-482%), fast response/recovery (200 ms/200 ms) and favorable reliability and reproducibility over 1000 cycles. Besides, the constructed Hf-SiO2 coating also makes the sensor exhibit excellent superhydrophobicity, self-cleaning property, and corrosion-resistance. As a proof of concept, our prepared high-performance strain sensor can realize the full-range monitoring of human motions and physiological signals even in the water environment, including pulse, vocalization, joint bending, running, and gesture recognition. Interestingly, it can also be knitted into a tactile electronic textile for spatial pressure distribution measurement. Thus, this study provides a universal technique for the preparation of high-performance strain sensors with great potential applications in the field of next-generation intelligent wearable electronics.

Acidity-Activatable Nanoparticles with Glucose Oxidase-Enhanced Photoacoustic Imaging and Photothermal Effect, and Macrophage-Related Immunomodulation for Synergistic Treatment of Biofilm Infection.

The pH-responsive theragnostics exhibit great potential for precision diagnosis and treatment of diseases. Herein, acidity-activatable nanoparticles of GB@P based on glucose oxidase (GO) and polyaniline are developed for treatment of biofilm infection. Catalyzed by GO, GB@P triggers the conversion of glucose into gluconic acid and hydrogen peroxide (H2 O2 ), enabling an acidic microenvironment-activated simultaneously enhanced photothermal (PT) effect/amplified photoacoustic imaging (PAI). The synergistic effects of the enhanced PT efficacy of GB@P and H2 O2 accelerate biofilm eradication because the penetration of H2 O2 into biofilm improves the bacterial sensitivity to heat, and the enhanced PT effect destroys the expressions of extracellular DNA and genomic DNA, resulting in biofilm destruction and bacterial death. Importantly, GB@P facilitates the polarization of proinflammatory M1 macrophages that initiates macrophage-related immunity, which enhances the phagocytosis of macrophages and secretion of proinflammatory cytokines, leading to a sustained bactericidal effect and biofilm eradication by the innate immunomodulatory effect. Accordingly, the nanoplatform of GB@P exhibits the synergistic effects on the biofilm eradication and bacterial residuals clearance through a combination of the enhanced PT effect with immunomodulation. This study provides a promising nanoplatform with enhanced PT efficacy and amplified PAI for diagnosis and treatment of biofilm infection.

Bone regeneration materials and their application over 20 years: A bibliometric study and systematic review.

Bone regeneration materials (BRMs) bring us new sights into the clinical management bone defects. With advances in BRMs technologies, new strategies are emerging to promote bone regeneration. The aim of this study was to comprehensively assess the existing research and recent progress on BRMs, thus providing useful insights into contemporary research, as well as to explore potential future directions within the scope of bone regeneration therapy. A comprehensive literature review using formal data mining procedures was performed to explore the global trends of selected areas of research for the past 20 years. The study applied bibliometric methods and knowledge visualization techniques to identify and investigate publications based on the publication year (between 2002 and 2021), document type, language, country, institution, author, journal, keywords, and citation number. The most productive countries were China, United States, and Italy. The most prolific journal in the BRM field was Acta Biomaterialia, closely followed by Biomaterials. Moreover, recent investigations have been focused on extracellular matrices (ECMs) (370 publications), hydrogel materials (286 publications), and drug delivery systems (220 publications). Research hotspots related to BRMs and extracellular matrices from 2002 to 2011 were growth factor, bone morphogenetic protein (BMP)-2, and mesenchymal stem cell (MSC), whereas after 2012 were composite scaffolds. Between 2002 and 2011, studies related to BRMs and hydrogels were focused on BMP-2, in vivo, and in vitro investigations, whereas it turned to the exploration of MSCs, mechanical properties, and osteogenic differentiation after 2012. Research hotspots related to BRM and drug delivery were fibroblast growth factor, mesoporous materials, and controlled release during 2002-2011, and electrospinning, antibacterial activity, and in vitro bioactivity after 2012. Overall, composite scaffolds, 3D printing technology, and antibacterial activity were found to have an important intersection within BRM investigations, representing relevant research fields for the future. Taken together, this extensive analysis highlights the existing literature and findings that advance scientific insights into bone tissue engineering and its subsequent applications.

Bioresponsive nano-antibacterials for H2S-sensitized hyperthermia and immunomodulation against refractory implant-related infections.

There is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial biofilm infections. Here, a novel "gas-sensitized hyperthermia" strategy is proposed for appreciable bacteria killing by the smart design of a metal-organic framework (MOF)-sealed Prussian blue-based nanocarrier (MSDG). Once the biofilm microenvironment (BME) is reached, the acidity-activated MOF degradation allows the release of diallyl trisulfide and subsequent glutathione-responsive generation of hydrogen sulfide (H2S) gas. Upon near-infrared irradiation, H2S-sensitized hyperthermia arising from MSDG can efficiently eliminate biofilms through H2S-induced extracellular DNA damage and heat-induced bacterial death. The generated H2S in the biofilm can stimulate the polarization of macrophages toward M2 phenotype for reshaping immune microenvironment. Subsequently, the secretion of abundant regeneration-related cytokines from M2 macrophages accelerates tissue regeneration by reversing the infection-induced pro-inflammatory environment in an implant-related infection model. Collectively, such BME-responsive nano-antibacterials can achieve biofilm-specific H2S-sensitized thermal eradiation and immunomodulatory tissue remodeling, thus realizing the renaissance of precision treatment of refractory implant-related infections.

A Tissue-Like Soft All-Hydrogel Battery.

To develop wearable and implantable bioelectronics accommodating the dynamic and uneven biological tissues and reducing undesired immune responses, it is critical to adopt batteries with matched mechanical properties with tissues as power sources. However, the batteries available cannot reach the softness of tissues due to the high Young's moduli of components (e.g., metals, carbon materials, conductive polymers, or composite materials). The fabrication of tissue-like soft batteries thus remains a challenge. Here, the first ultrasoft batteries totally based on hydrogels are reported. The ultrasoft batteries exhibit Young's moduli of 80 kPa, perfectly matching skin and organs (e.g., heart). The high specific capacities of 82 mAh g-1 in all-hydrogel lithium-ion batteries and 370 mAh g-1 in all-hydrogel zinc-ion batteries at a current density of 0.5 A g-1 are achieved. Both high stability and biocompatibility of the all-hydrogel batteries have been demonstrated upon the applications of wearable and implantable. This work illuminates a pathway for designing power sources for wearable and implantable electronics with matched mechanical properties.

Multiplexing Nanodrug Ameliorates Liver Fibrosis via ROS Elimination and Inflammation Suppression.

Liver fibrosis is the leading risk factor for hepatocellular carcinoma. Both oxidative stress and inflammation promote the progression of liver fibrosis, but existing therapeutic strategies tend to focus solely on one issue. Additionally, targeting of pathological microstructures is often neglected. Herein, an esterase-responsive carbon quantum dot-dexamethasone (CD-Dex) is developed for liver fibrosis therapy to simultaneously target pathological microstructures, scavenge reactive oxygen species (ROS), and suppress inflammation. Hepatocyte-targeting CD-Dex can efficiently eliminate the intrahepatic ROS, thereby inhibiting the activation of Kupffer cells, preventing further inflammation progression. Moreover, released dexamethasone (Dex) also suppresses inflammatory response by inhibiting the infiltration of inflammatory cells. Antifibrotic experiments demonstrate that CD-Dex significantly alleviates liver injury and collagen deposition, consequently preventing the progression of liver fibrosis. Taken together, these findings suggest that via ROS elimination and inflammation suppression, the newly developed multiplexing nanodrug exhibits great potential in liver fibrosis therapy.

Modified Alginate-Based Hydrogel as a Carrier of the CB2 Agonist JWH133 for Bone Engineering.

Alginate hydrogels have been widely used as excellent scaffold materials for implantation in biological systems because of their good biocompatibility. However, it is difficult to repair bone defects with these materials because of their poor mechanical properties. The aim of the present study was to fabricate a novel degradable alginate/palygorskite (PAL) composite hydrogel with good mechanical properties and investigate its potential for application in bone defect repair. The modified alginate-based hydrogel with increasing PAL content exhibited better mechanical properties than the original alginate hydrogel. In addition, the resulting composite hydrogel was thoroughly characterized by scanning electron microscopy (SEM). With increasing PAL content, the swelling ratio of the hydrogel increased in PBS (pH = 7.4). In vitro cytocompatibility was evaluated using bone marrow-derived mesenchymal stem cells (BMSCs) to confirm that the developed composite hydrogel was cytocompatible after 1, 3, and 7 days. All these results suggest that the developed composite hydrogel has great potential for bone tissue engineering applications. JWH133 is a selective agonist of cannabinoid receptor type 2 (CB2), which exerts dual anti-inflammatory and anti-osteoclastogenic effects. We co-cultured BMSCs with composite hydrogels loaded with JWH133, and analysis of proliferation and osteogenic differentiation indicated that the composite hydrogel loaded with JWH133 may enhance the osteogenic differentiation of rat BMSCs. Furthermore, we found that the composite hydrogel loaded with JWH133 inhibited osteoclast formation and the mRNA expression of osteoclast-specific markers. In summary, the developed composite hydrogel has a high drug-loading capacity, good biocompatibility, and strong potential as a drug carrier for treating osteoporosis by promoting osteoblast and inhibiting osteoclast formation and function.

Multifunctional Magnetic Ti3C2Tx MXene/Graphene Aerogel with Superior Electromagnetic Wave Absorption Performance.

Ingenious microstructure design and a suitable multicomponent strategy are still challenging for advanced electromagnetic wave absorbing (EMA) materials with strong absorption and a broad effective absorption bandwidth (EAB) at thin sample thickness and low filling level. Herein, a three-dimensional (3D) dielectric Ti3C2Tx MXene/reduced graphene oxide (RGO) aerogel anchored with magnetic Ni nanochains was constructed via a directional-freezing method followed by the hydrazine vapor reduction process. The oriented cell structure and heterogeneous dielectric/magnetic interfaces benefit the superior absorption performance by forming perfect impedance matching, multiple polarizations, and electric/magnetic-coupling effects. Interestingly, the prepared ultralight Ni/MXene/RGO (NiMR-H) aerogel (6.45 mg cm-3) delivers the best EMA performance in reported MXene-based absorbing materials up to now, with a minimal reflection loss (RLmin) of -75.2 dB (99.999 996% wave absorption) and a broadest EAB of 7.3 GHz. Furthermore, the excellent structural robustness and mechanical properties, as well as the high hydrophobicity and heat insulation performance (close to air), guarantee the stable and durable EMA application of the NiMR-H aerogel to resist deformation, water or humid environments, and high-temperature attacks.

Decylubiquinone suppresses breast cancer growth and metastasis by inhibiting angiogenesis via the ROS/p53/ BAI1 signaling pathway.

Breast cancer is one of the most common cancers worldwide with a rising incidence, and is the leading cause of cancer-related death among females. Angiogenesis plays an important role in breast cancer growth and metastasis. In this study, we identify decylubiquinone (DUb), a coenzyme Q10 analog, as a promising anti-breast cancer agent through suppressing tumor-induced angiogenesis. We screened a library comprising FDA-approved drugs and found that DUb significantly inhibits blood vessel formation using in vivo chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. DUb was further identified to inhibit angiogenesis in the rat aortic ring and Matrigel plug assay. Moreover, DUb was found to suppress breast cancer growth and metastasis in the MMTV-PyMT transgenic mouse and human xenograft tumor models. To explore whether the anticancer efficacy of DUb was directly corrected with tumor-induced angiogenesis, the MDA-MB-231 breast cancer assay on the CAM was performed. Interestingly, DUb significantly inhibits the angiogenesis of breast cancer on the CAM. Brain angiogenesis inhibitor 1 (BAI1), a member of the G protein-coupled receptor (GPCR) adhesion subfamily, has an important effect on the inhibition of angiogenesis. Further studies demonstrate that DUb suppresses the formation of tubular structures by regulating the reactive oxygen species (ROS)/p53/BAI1 signaling pathway. These results uncover a novel finding that DUb has the potential to be an effective agent for the treatment of breast cancer by inhibiting tumor-induced angiogenesis.

R5, a neutralizing antibody to Robo1, suppresses breast cancer growth and metastasis by inhibiting angiogenesis via down-regulating filamin A.

Breast cancer (BC) is one of the most common cancers among women in both developed and developing countries with a rising incidence. Using the MMTV-PyMT transgenic mouse model and xenografted breast cancer model, we found that R5, a neutralizing antibody to Robo1, significantly inhibited BC growth and metastasis. Angiogenesis is involved in the growth and metastasis of BC. Interestingly, R5 significantly decreases microvessel density in BC tissues, and inhibits blood vessel formation and development in in vivo chick embryo chorioallantoic membrane (CAM), yolk sac membrane (YSM) and Matrigel plug models. To investigate whether its anti-breast cancer efficacy is ascribed to its direct antiangiogenic properties, xenografted breast cancer model on CAM was established. Furthermore, R5 significantly reduces the tube formation of the vascular plexus on xenografted breast tumor on CAM. R5 also suppresses the migration and the tubular structure formation of human umbilical vein endothelial cells (HUVECs) by down-regulating the expression of filamin A (FLNA). These findings show that R5 has the potential to be a promising agent for the treatment of BC by suppressing the tumor-induced angiogenesis.