Ion-Sieve-Confined Synthesis of Size-Tunable Ru for Electrochemical Hydrogen Evolution.

The controllable and low-cost synthesis of nanometal particles is highly desired in scientific and industrial research. Herein, size-tunable Ru nanoparticles were synthesized by using a novel ion-sieve-confined reduction method. The H2TiO3 ion-sieve was used to adsorb Ru3+ into the hydroxyl-enriched porous [TiO3]2- layers. The confined environment of the interlayer space facilitates Ru-Ru collision and bonding during annealing, achieving a precise reduction from Ru3+ to Ru0 without additional reductants. Owing to the confinement effect, Ru0 nanoparticles are uniformly embedded in the pores on the surface of the postannealed TiO2 matrix (Ru@TiO2). Ru@TiO2 exhibited a lower overpotential than Pt/C (57 vs 87 mV at 10 mA cm-2) for the HER in 0.1 M KOH solution. The confinement-induced reduction of metal ions was also preliminarily proved in ion-exchanged zeolites, which provides facile and abundant approaches for the size-controllable synthesis of nanometal catalysts with high catalytic activity.

Efficacy of endoscopic mucosal resection versus endoscopic submucosal dissection for rectal neuroendocrine tumors ≤10mm: a systematic review and meta-analysis.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are surgical methods used for rectal neuroendocrine tumors (NETs) with diameters of ≤ 10 mm. However, which method has a higher performance remains uncertain. OBJECTIVES: Evaluate which of the two methods shows a higher performance. DESIGN: Systematic review and meta-analysis METHODS: Data from PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to 12 April 2022. Outcomes, including complete resection, en bloc resection, recurrence, perforation, bleeding, and procedure time, were pooled by 95% confidence intervals (95% CI) using a fixed- or random-effects model. MAIN OUTCOME MEASURES: Complete resection, en bloc resection, and recurrence. SAMPLE SIZE: 18 studies, including 1168 patients were included in the study. RESULTS: Eighteen retrospective cohort studies were included in this meta-analysis. There were no statistical differences in the rates of complete resection, en bloc resection, recurrence, perforation, and bleeding rates between EMR and ESD. However, a statistical difference was detected in the procedure time; EMR had a significantly shorter time (MD=-17.47, 95% CI=-22.31 - -12.62, P<.00001). CONCLUSIONS: EMR and ESD had similar efficacies and safety profiles in resectioning rectal NETs ≤ 10 mm. Even so, the advantages of EMR included a shorter operation time and expenditure. Thus, with respect to health economics, EMR outperformed ESD. LIMITATION: Most of these studies are retrospective cohort studies instead of RCTs. CONFLICT OF INTEREST: None.

Application of food exchange portion method in home-based nutritional intervention for elderly patients with chronic heart failure.

BACKGROUND: The home treatment of elderly patients with chronic heart failure (CHF) is often accompanied by malnutrition, which increases the risk of re-hospitalisation and affects the prognosis. Therefore, how to effectively improve the nutritional self-management of patients is a current focus of medical research. This study aims to test the effect of home-based nutritional intervention method on improving the nutritional status of elderly patients with CHF. METHODS: A total of 90 hospitalised elderly patients with CHF were randomly divided into the experimental group (n = 45) and the control group (n = 45). The patients in both groups were given standardised drug therapy and their nutritional status was evaluated using a body composition analyser prior to discharge (protein, body fat percentage, visceral fat area, skeletal muscle, upper arm muscle circumference, left lower limb and right lower limb muscle mass), with the cardiopulmonary function evaluated using a six-minute walk test and the metabolic equivalents method. The control group was given general nutrition education and routine dietary guidance from cardiac rehabilitation nurses, while the experimental group was given an individualised nutrition prescription by dietitians based on the evaluation results, according to which one-to-one food exchange dietary intervention training was given until the patients mastered the process. RESULTS: The nutritional indexes at the end of the study were significantly higher in the experimental group than in the control group and were higher than those before the intervention (P < 0.05). The muscle circumference of the upper arm, the muscle mass of the left lower limb and the right lower limb had no statistical significance following the intervention compared to the control group and before the intervention (P > 0.05). The cardiopulmonary function indexes were significantly better in the experimental group at the end of the study than before the intervention and were better than those in the control group, with statistically significant differences (P < 0.05), while no significant changes were observed in the control group before and after the intervention (P > 0.05). CONCLUSION: The home-based nutritional intervention method of food exchange portions can effectively improve the nutritional status of elderly patients with CHF, with the distribution of visceral fat more reasonable and the cardiopulmonary function and exercise endurance improved.

Simulating electric field and current density in nanostructured electrocatalysts.

The electrocatalytic performance of nanostructured heterogeneous electrocatalysts can be tailored by adjusting their geometries due to the morphologically dependent physicochemical effects, such as field-induced reagent concentration near high-curvature nanoscale features and the confinement of reaction intermediates in a nanocavity. However, the theoretical studies on these physicochemical effects in various nanoscale structures are considerably less common in comparison to the density functional theory calculations on the atomic structure design due to the absence of consistent simulation protocols in this area. This tutorial review presents the theory, models, and protocols for the simulation of the electrochemical properties of nanoelectrocatalysts with complex morphologies using the finite element method (FEM), including the local electric field (E-field) and the current density in the electrolyte adjacent to the electrode (Jelectrolyte) and in the electrode (Jelectrode). In the E-field simulation, we demonstrate the significant screening effect of the EDL on the E-field distribution as well as the influence of the relative permittivity of the electrolyte on the screening strength. In the Jelectrolyte simulation, we illustrate the impact of the electrode kinetics on the electron transfer, which can significantly affect the Jelectrolyte profile. In the Jelectrode simulation, we reveal that the Jelectrode crowding can occur in constricted areas of nanostructures, which would cause the structural transformation via electromigration. Finally, we discuss the applicability and limitations of the theoretical models discussed in this tutorial, suggesting the focus of future work to develop advanced multiscale modelling approaches. We hope this tutorial will assist electrochemists in navigating how to conduct accurate electrochemical physics effect simulations for analyzing the catalytic performance of nanoelectrocatalysts and thereby contribute to a wider adoption of FEM simulations in the rational design of advanced electrocatalysts.

Reaction-intermediate-induced atomic mobility in heterogeneous metal catalysts for electrochemical reduction of CO2.

Improving the activity and selectivity of heterogeneous metal electrocatalysts has been the primary focus of CO2 electroreduction studies, however, the stability of these materials crucial for practical application remains less understood. In our work, the impact of the reaction intermediates (RIs) on the energetics and mechanism of metal-atom migration is studied with a combination of density functional theory (DFT) and ab initio molecular dynamics (AIMD) on pure transition metals Cu, Ag, Au, Pd, as well as three Cu4-xPdx (x = 1,2, and 3) alloys. Reaction intermediates (RIs) for the CO2 reduction reaction, H2 evolution, and O2 reduction were considered. The effect of adsorbed RIs was observed to facilitate metal atom migration generally by decreasing the kinetic barriers for migration. The atomic mobility trends in the commonly used CO2RR metal electrocatalysts in the course of electrolysis conditions were established. This study provides theoretical insight into understanding how the electrocatalyst may undergo promoted restructuring in the presence of RIs under realistic electrochemical conditions.

Alloying Motif Confined in Intercalative Frameworks toward Rapid Li-Ion Storage.

High-capacity alloying-type anodes suffer poor rate capability due to their great volume expansion, while high-rate intercalation-type anodes are troubled with low theoretical capacity. Herein, a novel mechanism of alloying in the intercalative frameworks is proposed to confer both high-capacity and high-rate performances on anodes. Taking the indium-vanadium oxide (IVO) as a typical system, alloying-typed In is dispersed in the stable intercalative V2 O3 to form a solid solution. The alloying-typed In element provides high lithium storage capacity, while the robust, Li-conductive V-O frameworks effectively alleviate the volume expansion and aggregation of In. Benefiting from the above merits, the anode exhibits a high specific capacity of 1364 mA h g-1 at 1 A g-1 and an extraordinary cyclic performance of 814 mA h g-1 at 10 A g-1 after 600 cycles (124.9 mA h g-1 after 10 000 cycles at 50 A g-1 ). The superior electrochemical rate capability of (In,V)2 O3 solid solution anode rivals that of the reported alloying anode materials. This strategy can be extended for fabricating other alloying/intercalation hybrid anodes, such as (Sn,V)O2 and (Sn,Ti)O2 , which demonstrates the universality of confining alloying motifs in intercalative frameworks for rapid and high-capacity lithium storage.

Stochastic Binding Dynamics of a Photoswitchable Single Supramolecular Complex.

In this work, a real-time precise electrical method to directly monitor the stochastic binding dynamics of a single supramolecule based on the host-guest interaction between a cyclodextrin and an azo compound is reported. Different intermolecular binding states during the binding process are distinguished by conductance signals detected from graphene-molecule-graphene single-molecule junctions. In combination with theoretical calculations, the reciprocating and unidirectional motions in the trans form as well as the restrained reciprocating motion in the cis form due to the steric hindrance is observed, which could be reversibly switched by visible and UV irradiation. The integration of individual supramolecules into nanocircuits not only offers a facile and effective strategy to probe the dynamic process of supramolecular systems, but also paves the way to construct functional molecular devices toward real applications such as switches, sensors, and logic devices.

Active Ingredients and Potential Mechanisms of the Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction against Ulcerative Colitis: A Network Pharmacology and Molecular Docking-Based Study.

BACKGROUND: Ulcerative colitis (UC), a chronic and nonspecific inflammatory bowel disease, seriously affects the quality of patients' life. Han Re Bing Yong Fa (treating diseases with both cool- and warm-natured herbs) is a classical therapeutic principle of traditional Chinese medicine (TCM), which is often used to treat chronic diseases, including UC. The Gan Jiang-Huang Qin-Huang Lian-Ren Shen decoction (GJHQHLRSD), a representative of Han Re Bing Yong Fa, is effective in alleviating inflammatory symptoms in UC. However, the pharmacological mechanism underlying its anti-inflammatory effect remains unclear. METHODS: A network pharmacology strategy, including the construction and analysis of the drug-disease network, was used to explore the complex mechanism of GJHQHLRSD treatment of UC. In addition, molecular docking technology was used to preliminarily examine the binding ability of the potential active components and core therapeutic targets of GJHQHLRSD. RESULTS: The network pharmacology results revealed 140 targets of GJHQHLRSD which are involved in UC. The PPI network analysis identified seven target genes: BCL2L1, NR3C1, ALOX5, S1PR5, NR1I2, CYP2D6, and LPAR6. The molecular docking results revealed that the following displayed strongest combined effects: EGFR with kaempferol, ERK1 with worenine, STAT3 with Palmidin A, BCL2L1 with diop and VEGFA with ginsenoside Rg3. The KEGG and gene ontology enrichment analyses results indicated that GJHQHLRSD functions by regulating the EGFR signaling pathway in UC treatment. Other effective biological processes involved in UC treatment included cancer-related as well as inflammation and viral infection signaling pathways, such as the "MicroRNAs in cancer," "TNF signaling pathway," and "JAK-STAT signaling pathway." CONCLUSIONS: This study reflects the multicomponent, multitarget, and multipathway characteristics of the action mechanism of GJHQHLRSD in treating UC. Furthermore, it helps better understand the TCM therapeutic principle of Han Re Bing Yong Fa and explore novel candidate drug targets for UC treatment.

Enhanced Transmission from Visible to Terahertz in ZnTe Crystals with Scalable Subwavelength Structures.

The zinc blend nonlinear crystal of zinc telluride (ZnTe) is currently one of the most commonly used electro-optical material for terahertz (THz) probe and imaging. We report herein how to engineer the surface behavior of a ZnTe single crystal to design subwavelength structures (SWSs) for enhancing ultrabroadband transmission. Polystyrene (PS) nanoparticle monolayers with a maximum coverage of 85.2% were produced on the ZnTe crystal by an eccentric spin-coating technique combined with surface wettability engineering. Subsequently, the well-defined conical SWS arrays were fabricated on the ZnTe crystal by reactive ion etching over the PS monolayer template, with the size of the SWS arrays customized by optimizing the etching process. Finally, we demonstrated ultrabroadband antireflection on the surface structured ZnTe crystals in the visible-near-infrared, infrared, and terahertz regions with transmittance increase of 11.6%, 10.0%, and 24.8%, which are attributed to the decrease of surface Fresnel reflection by SWS. Notably, in 0.2-1.0 THz, the transmittance reached over 70%. Our work provides a new strategy to enhance the THz generation efficiency and detection sensitivity based on ZnTe crystals by surface engineering.

Cross-talk Between Histone and DNA Methylation Mediates Bone Loss in Hind Limb Unloading.

Bone loss induced by mechanical unloading is a common skeletal disease, but the precise mechanism remains unclear. The current study investigated the role of histone methylation, a key epigenetic marker, and its cross-talk with DNA methylation in bone loss induced by mechanical unloading. The expression of G9a, ubiquitin-like with PHD and ring finger domains 1 (UHRF1), and DNA methylation transferase 1 (DNMT1) were increased in hind limb unloading (HLU) rats. This was accompanied by an increased level of histone H3 lysine 9 (H3K9) di-/tri-methylation at lncH19 promoter. Then, alteration of G9a, DNMT1, or UHRF1 expression significantly affected lncH19 level and osteogenic activity in UMR106 cells. Osteogenic gene expression and matrix mineralization were robustly promoted after simultaneous knockdown of G9a, DNMT1, and UHRF1. Furthermore, physical interactions of lncH19 promoter with G9a and DNMT1, as well as direct interactions among DNMT1, G9a, and UHRF1 were detected. Importantly, overexpression of DNMT1, G9a, or UHRF1, respectively, resulted in enrichment of H3K9me2/me3 and 5-methylcytosine at lncH19 promoter. Finally, in vivo rescue experiments indicated that knockdown of DNMT1, G9a, or UHRF1 significantly relieved bone loss in HLU rats. In conclusion, our research demonstrated the critical role of H3K9 methylation and its cross-talk with DNA methylation in regulating lncH19 expression and bone loss in HLU rats. Combined targeting of DNMT1, G9a, and UHRF1 could be a promising strategy for the treatment of bone loss induced by mechanical unloading. © 2021 American Society for Bone and Mineral Research (ASBMR).

Iron chelation promotes 5-aminolaevulinic acid-based photodynamic therapy against oral tongue squamous cell carcinoma.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is the most common malignancy of the oral cavity. Photodynamic therapy (PDT) has become a clinically promising approach for early stage OTSCC treatment. 5-Aminolaevulinic acid (5-ALA) is a precursor of protoporphyrin IX (PpIX) and has been applied for PDT of cancer. However, the accumulated PpIX in 5-ALA-treated cancer cells will be further transformed into heme through ferrous iron insertion under ferrochelatase catalysis. Theoretically, iron chelation can enhance the intracellular accumulation of PpIX and thus promote 5-ALA-based PDT. Here, an iron chelator deferasirox (DFX) was used to investigate synergistic suppression effects of 5-ALA-based PDT and iron chelation on OTSCC. METHODS: In OTSCC SCC-25 cells, the enhancing effect of DFX on 5-ALA-mediated accumulation of PpIX was firstly assessed. After laser irradiation (635 nm, 200 mW/cm2 and 2 min), the synergistic cytotoxicity and apoptosis-inducing effect of 5-ALA and DFX were evaluated in SCC-25 cells, and the apoptosis mechanism was further investigated by monitoring the change of mitochondrial membrane potential and observing the subcellular localization of cytochrome c (Cyt c). In SCC-25 tumor-bearing mice, the synergistic suppression effects of 5-ALA-based PDT and DFX on tumor growth and tumor angiogenesis were investigated after laser irradiation on the tumor (635 nm, 150 mW/cm2 and 10 min). RESULTS: In SCC-25 cells, DFX showed strong iron chelation effect and enhanced 5-ALA-mediated intracellular accumulation of PpIX by 2-3 folds. After laser irradiation (635 nm, 200 mW/cm2 and 2 min), 5-ALA combined with DFX exhibited significant synergistic effects on cytotoxicity and cell apoptosis. In the treated cells, the damage of mitochondrial membrane and the release of Cyt c from mitochondria to cytoplasm were observed distinctly, indicating the activation of mitochondria-related signal pathway. In SCC-25 tumor-bearing mice, tumor growth and tumor angiogenesis were both notably suppressed by combination treatment of 5-ALA with laser irradiation and DFX. Meanwhile, no obvious toxic injuries were visible in histological examination of major organs in the treated mice. CONCLUSIONS: 5-ALA-based PDT combined with iron chelation synergistically inhibited the growth of OTSCC. Hence it can be seen that this combination therapy may represent a promising strategy for clinical treatment of OTSCC and other cancers.

The application of the scallop nanostructure in deep silicon etching.

Micro/nanostructures with high aspect ratios in silicon wafers obtained by plasma etching are of great significance in device fabrication. In most cases, the scallop nanostructure in deep silicon etching should be suppressed. However, the scallop nanostructure could be applied in electronic device fabrication as characteristic information, which indicates the balance between deposition and etching. In this work, the applications of scallop nanostructures in etching process optimization and environmental protection are demonstrated. In addition, the minimum effect of the cycle time on the scallop size is reported for the first time. These results could bring new thoughts to the electronic devices related fields, such as micro-electro-mechanical systems (MEMS), silicon capacitors and advanced packaging.

Measuring Electronic Spectra of Differential Mobility-Selected Ions in the Gas Phase.

We describe the modification of a commercially available tandem differential mobility mass spectrometer (DMS) that has been retrofitted to facilitate photodissociation (PD) of differential mobility-separated, mass-selected molecular ions. We first show that a mixture of protonated quinoline/isoquinoline (QH+/iQH+) can be separated using differential mobility spectrometry. Efficient separation is facilitated by addition of methanol to the DMS environment and increased residence time within the DMS. In action spectroscopy experiments, we gate each isomer using appropriate DMS settings, trap the ions in the third quadrupole of a triple quadrupole mass spectrometer, and irradiate them with tunable light from an optical parametric oscillator (OPO). The resulting mass spectra are recorded as the OPO wavelength is scanned, giving PD action spectra. We compare our PD spectra with previously recorded spectra for the same species and show that our instrument reproduces previous works faithfully.

Fluorometric determination of aflatoxin B1 using a labeled aptamer and gold nanoparticles modified with a complementary sequence acting as a quencher.

A fluorometric aptamer based assay is described for rapid and sensitive detection of aflatoxin B1 (AFB1). It is making use of a fluorescein (FAM) labeled anti-AFB1 aptamer and complementary DNA-modified gold nanoparticles (GNPs). In the absence of AFB1, the FAM-labeled aptamers hybridize with complementary DNA strands that were covalently immobilized on GNPs. This results in quenching of the green fluorescence (with excitation/emission peaks at 485/525 nm). In the presence of AFB1, the aptamer probe binds AFB1 and is released from the GNPs. Hence, fluorescence is restored. Under optimized conditions, AFB1 in the concentration range from 61 pM to 4.0 µM can be detected, and the detection limit is 61 pM. This assay is highly selective for AFB1. It was applied to the determination of AFB1 spiked into 50-fold diluted wine and 20-fold diluted beer. Graphical abstract Schematic presentation of fluorometric detection of AFB1 using a fluorescein (FAM) labeled anti-AFB1 aptamer and complementary DNA-modified gold nanoparticles (GNPs).

Augmenting Basin-Hopping With Techniques From Unsupervised Machine Learning: Applications in Spectroscopy and Ion Mobility.

Evolutionary algorithms such as the basin-hopping (BH) algorithm have proven to be useful for difficult non-linear optimization problems with multiple modalities and variables. Applications of these algorithms range from characterization of molecular states in statistical physics and molecular biology to geometric packing problems. A key feature of BH is the fact that one can generate a coarse-grained mapping of a potential energy surface (PES) in terms of local minima. These results can then be utilized to gain insights into molecular dynamics and thermodynamic properties. Here we describe how one can employ concepts from unsupervised machine learning to augment BH PES searches to more efficiently identify local minima and the transition states connecting them. Specifically, we introduce the concepts of similarity indices, hierarchical clustering, and multidimensional scaling to the BH methodology. These same machine learning techniques can be used as tools for interpreting and rationalizing experimental results from spectroscopic and ion mobility investigations (e.g., spectral assignment, dynamic collision cross sections). We exemplify this in two case studies: (1) assigning the infrared multiple photon dissociation spectrum of the protonated serine dimer and (2) determining the temperature-dependent collision cross-section of protonated alanine tripeptide.

Production of High Internal Phase Emulsion with a Miniature Twin Screw Extruder.

Emulsions are traditionally prepared by batched emulsifying an oil phase and aqueous phase with a magnetic/mechanical stirrer, homogenizer, or ultrasonic machine, etc. Herein, high internal phase emulsions (HIPEs) produced with a miniature twin screw extruder were first investigated. Adding an oil phase (the mixture of styrene, divinylbenzene, and span 80) and aqueous phase to the inlet of a miniature twin screw extruder, a series of white and viscous HIPEs were obtained at the outlet of the extruder. With the screw rotation speed and the surfactant content varied respectively in the ranges of 50-200 rpm and 5-20%, a series of HIPEs having uniform droplet size were produced. Polymerizing these HIPEs caused a series of polymerized HIPES, which have a well-defined open-cell structure. The method developed herein shows that it is possible to prepare emulsions with oil and water by twin screw extrusion. Also, it may also cause a continuous preparation of HIPEs when the miniature twin screw extruder was replaced by an industrial extruder.

Glutamine-ß-cyclodextrin for targeted doxorubicin delivery to triple-negative breast cancer tumors via the transporter ASCT2.

Chemotherapy is the primary therapy for triple-negative breast cancer (TNBC) and the tumor-targeted delivery of chemotherapeutic drugs is necessary to minimize their side effects on normal tissues. TNBC cells display addictions to glutamine in culture, and the levels of the glutamine transporter, alanine-serine-cysteine transporter 2 (ASCT2), are elevated in many types of cancer. However, glutamine- or ASCT2-based carriers have not been used in tumor-targeted drug delivery. In this study, a novel derivative of ß-cyclodextrin (ß-CD), glutamine-ß-cyclodextrin (GLN-CD), was developed by conjugating glutamine with the 6-hydroxy of ß-CD, and GLN-CD was then used to prepare doxorubicin (DOX) inclusion complexes (DOX@GLN-CD) for TNBC treatment. GLN-CD and glutamine have similar ASCT2-binding sites, and GLN-CD has the potential to enter cells through ASCT2-dependent facilitated diffusion. An increase in the degree of substitution did not promote binding between GLN-CD and ASCT2. GLN-CD and DOX formed inclusion complexes at a molar ratio of 1 : 1. DOX@GLN-CD specifically accumulated in TNBC cells, including MDA-MB-231 and BT549 cells, where it subsequently induced G2/M blockade and apoptosis, but hardly affected nontumorigenic MCF10A cells. l-γ-Glutamyl-p-nitroanilide (GPNA), which is a specific inhibitor of ASCT2, antagonistically decreased the cellular uptake of DOX@GLN-CD by TNBC cells, which further confirmed the role of ASCT2 in DOX@GLN-CD transport. In vivo, DOX@GLN-CD accumulated specifically in tumors, achieved improved outcomes and minimized the toxic effects on main organs at the same dose as DOX. As a novel derivative of ß-CD, GLN-CD is an effective carrier that can specifically deliver DOX to TNBC cells via targeting ASCT2 and minimize its uptake by normal cells.

Multifunctional nanoparticles based on a polymeric copper chelator for combination treatment of metastatic breast cancer.

Copper plays an important role in tumor growth and metastasis. Copper chelation has been confirmed to be an effective strategy for breast cancer therapy through antiangiogenesis. In this work, a copper chelating coil-comb block copolymer RGD-PEG-b-PGA-g-(TETA-DTC-PHis) (RPTDH) was synthesized and used to prepare nanoparticles for loading resiquimod (R848), a TLR7 and TLR8 agonist, thus to combine antiangiogenesis and immune activation to treat breast cancer. RPTDH has strong copper-chelating ability and could self-assemble to form spherical nanoparticles with significant pH-sensitivity. R848 was efficiently loaded into RPTDH nanoparticles and exhibited greatly accelerated releases in weakly acid media simulating tumor microenvironment. RPTDH/R848 nanoparticles significantly inhibited the mobility, invasion and vascular tube formation of HUVECs via copper chelation, demonstrating their strong antiangiogenic activity in vitro. Furthermore, RPTDH/R848 nanoparticles remarkably induced the maturation and activation of human plasmacytoid dendritic CAL-1 cells, indicating their immune-activation ability. In breast tumor-bearing mice, RPTDH/R848 nanoparticles displayed excellent targeting ability for both primary breast tumor and lung metastases, and furthermore dramatically suppressed tumor growth and metastasis through copper deficiency-triggered antiangiogenesis and R848-induced immune activation. In summary, RPTDH/R848 nanoparticles can be used as an therapeutic agent against metastatic breast cancer through combining antiangiogenesis and immune activation.