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Fe-based 2D materials exhibit rich chemical compositions and structures, which may imply many unique physical properties and promising applications. However, achieving controllable preparation of ultrathin non-layered FeS crystal on SiO2/Si substrate remains a challenge. Herein, the influence of temperature and molecular sieves is reported on the synthesis of ultrathin FeS nanosheets with a thickness as low as 2.3 nm by molecular sieves-assisted chemical vapor deposition (CVD). The grown FeS nanosheets exhibit a non-layered hexagonal NiAs structure and belong to the P63/mmc space group. The inverted symmetry broken structure is confirmed by the angle-resolved second harmonic generation (SHG) test. In particular, the 2D FeS nanosheets exhibit exceptional metallic behavior, with conductivity up to 1.63 × 106 S m-1 at 300 K for an 8 nm thick sample, which is higher than that of reported 2D metallic materials. This work provides a significant contribution to the synthesis and characterization of 2D non-layered Fe-based materials.
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Introduction: Traditional/ritual/medical circumcision can be associated with considerable intraoperative blood loss and a prolonged postoperative healing course. This study investigated the feasibility of the magnetic compression technique (MCT) for circumcision in beagle dogs. Methods: A set of magnetic rings including a daughter magnetic ring (DMR) and a parent magnetic ring (PMR) were designed for circumcision. In eight beagle dogs as the animal model, the DMR was placed between the penis and the foreskin through the glans, and then the PMR was placed outside the penis. The DMR and PMR automatically attracted together to compress the foreskin. The necrosis of the prepuce of the anterior penis was observed daily. The operation time and time to magnetic ring shedding were recorded. Healing of the foreskin stump was visually observed. Results: The magnetic rings were successfully installed in all eight dogs, and the operation process was without complication. The average operation time was 3.13 ± 0.92 min (range, 2-4.5 min). Postoperative X-rays showed good attraction of the magnetic rings. Daily post-operative observation showed progressive ischemic necrosis of the anterior foreskin and mild edema of the proximal foreskin. The dogs were generally in good condition and urinated freely. The magnetic rings fell off spontaneously 8-12 days after the operation, and the stump of the foreskin healed well. Conclusion: The MCT may be a new approach for circumcision in a canine model, which suggests its potential for use in humans.
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We present a facile and ultrafast mechanosynthesis of hydrogen-bonded organic frameworks |C10N2H10âHC2O4|2 with UV and NIR bidirectional photoswitching of photochromic/photothermal behavior. The reaction time is reduced to mere seconds, and the method is both high-yield and scalable.
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Multimetal phosphides derived from metal-organic frameworks (MOFs) have garnered significant interest owing to their distinct electronic configurations and abundant active sites. However, developing robust and efficient catalysts based on metal phosphides for overall water splitting (OWS) remains challenging. Herein, we present an approach for synthesizing a self-supporting hollow porous cubic FeNiP-CoP@NC catalyst on a nickel foam (NF) substrate. Through ion exchange, the reconstruction chemistry transforms the FeNi-MOF nanospheres into intricate hollow porous FeNi-MOF-Co nanocubes. After phosphorization, numerous N, P co-doped carbon-coated FeNiP-CoP nanoparticles were tightly embedded within a two-dimensional (2D) carbon matrix. The NF/FeNiP-CoP@NC heterostructure retained a porous configuration, numerous heterogeneous interfaces, distinct defects, and a rich composition of active sites. Moreover, incorporating Co and the resulting structural evolution facilitated the electron transfer in FeNiP-CoP@NC, enhancing the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) processes. Consequently, the NF/FeNiP-CoP@NC catalyst demonstrated very low overpotentials of 78 mV for OER and 254 mV for HER in an alkaline medium. It also exhibited excellent long-term stability at various potentials (@10 mA cm-2, @20 mA cm-2, and @50 mA cm-2). As an overall water splitting cell, it required only 1.478 V to drive a current density of 50 mA cm-2 and demonstrated long-term stability. Density functional theory (DFT) calculations revealed a synergistic effect between multimetal phosphides, enhancing the intrinsic OER and HER activities of FeNiP-CoP@NC. This work not only elucidates the role of heteroatom induction in structural reconstruction but also highlights the importance of electronic structure modulation.
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The excellent dielectric properties and tunable structural design of metal sulfides have attracted considerable interest in realizing electromagnetic wave (EMW) absorption. However, compared with traditional monometallic and bimetallic sulfides that are extensively studied, the unique physical characteristics of solid-solution-type sulfides in response to EMW have not been revealed yet. Herein, a unique method for preparing high-purity solid-solution-type sulfides is proposed based on solid-phase in situ exsolution of different metal ions from hybrid precursors. Utilizing CoAl-LDH/MIL-88A composite as a precursor, Fe0.8Co0.2S single-phase nanoparticles are uniformly in situ formed on an amorphous substrate (denoted as CoAl), forming CoAl/Fe0.8Co0.2S heterostructure. Combing with density functional theory (DFT) calculations and wave absorption simulations, it is revealed that Fe0.8Co0.2S solid solution has stronger intracrystal polarization and electronic conductivity than traditional monometallic and bimetallic sulfides, which lead to higher dielectric properties in EM field. Therefore, CoAl/Fe0.8Co0.2S heterostructure exhibits significantly enhanced EMW absorption ability in the low-frequency region (2-6 GHz) and can achieve frequency screening by selectively absorbing EMW of specific frequency. This work not only provides a unique method for preparing high-purity solid-solution-type sulfides but also fundamentally reveals the physical essence of their excellent EMW absorption performance.
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Cancer vaccine is regarded as an effective immunotherapy approach mediated by dendritic cells (DCs) which are crucial for antigen presentation and the initiation of adaptive immune responses. However, lack of DC-targeting properties significantly hampers the efficacy of cancer vaccines. Here, by using the phage display technique, peptides targeting the endocytic receptor DEC-205 primarily found on cDC1s were initially screened. An optimized hydrolysis-resistant peptide, hr-8, was identified and conjugated to PLGA-loaded antigen (Ag) and CpG adjuvant nanoparticles, resulting in a DC-targeting nanovaccine. The nanovaccine hr-8-PLGA@Ag/CpG facilitates dendritic cell maturation and improves antigen cross-presentation. The nanovaccine can enhance the antitumor immune response mediated by CD8+ T cells by encapsulating the nanovaccine with either exogenous OVA protein antigen or endogenous gp100/E7 antigenic peptide. As a result, strong antitumor effects are observed in both anti-PD-1 responsive B16-OVA and anti-PD-1 non-responsive B16 and TC1 immunocompetent tumor models. In summary, this study presents the initial documentation of a nanovaccine that targets dendritic cells via the novel DEC-205 binding peptide. This approach offers a new method for developing cancer vaccines that can potentially improve the effectiveness of cancer immunotherapy.
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Crohn's disease (CD) is a refractory chronic inflammatory bowel disease (IBD) with unknown etiology. Transmural inflammation, involving the intestine and mesentery, represents a characteristic pathological feature of CD and serves as a critical contributor to its intractability. Here, this study describes an oral pyroptosis nanoinhibitor loaded with tumor necrosis factor-α (TNF-α) deoxyribozymes (DNAzymes) (DNAzymes@degradable silicon nanoparticles@Mannose, Dz@MDSN), which can target macrophages at the site of inflammation and respond to reactive oxygen species (ROS) to release drugs. Dz@MDSN can not only break the inflammatory cycle in macrophages by degrading TNF-α mRNA but also reduce the production of ROS mainly from macrophages. Moreover, Dz@MDSN inhibits excessive pyroptosis in epithelial cells through ROS clearance, thereby repairing the intestinal barrier and reducing the translocation of intestinal bacteria to the mesentery. Consequently, these combined actions synergistically contribute to the suppression of inflammation within both the intestine and the mesentery. This study likely represents the first successful attempt in the field of utilizing nanomaterials to achieve transmural healing for CD, which also provides a promising treatment strategy for CD patients.
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Doença de Crohn , DNA Catalítico , Piroptose , Fator de Necrose Tumoral alfa , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Doença de Crohn/metabolismo , Piroptose/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Animais , Administração Oral , Camundongos , DNA Catalítico/química , DNA Catalítico/metabolismo , DNA Catalítico/farmacologia , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Silício/química , Silício/farmacologia , Manose/química , Manose/farmacologia , Células RAW 264.7 , MasculinoRESUMO
Zeolitic imidazolate framework-8 (ZIF-8) encapsulating enzymatically active biomolecules has emerged as a novel biocompatible nanozyme and offers significant implications for bioanalysis of various biomarkers towards early diagnosis of severe diseases such as cancers. However, the rapid, continuous and scalable synthesis of these nanozymes still remains challenging. In this work, we proposed a novel microfluidic approach for rapid and continuous synthesis of hemin@ZIF-8 nanozyme. By employing a distinctive combination of zigzag-shaped channel and spiral channel with sudden expansion structures, we have enhanced the mixing efficiency within the chip and achieved effective encapsulation of hemin in ZIF-8. The resulting hemin@ZIF-8 nanoparticles exhibit peroxidase-like activity and are capable of detecting free H2O2 with a limit of detection (LOD) as low as 45 nM, as well as H2O2 secreted by viable cells with a detection threshold of approximately 10 cells per mL. By leveraging this method, we achieved successful detection of cancer cells and effective screening of anticancer drugs that induce oxidative stress injury in cancer cells. This innovative microfluidic strategy offers a new avenue for synthesizing functional nanocomposites to facilitate the development of next-generation diagnostic tools for early disease detection and personalized medicine.
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Antineoplásicos , Hemina , Estruturas Metalorgânicas , Espécies Reativas de Oxigênio , Hemina/química , Hemina/metabolismo , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/análise , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/farmacologia , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Técnicas Analíticas Microfluídicas/instrumentação , Ensaios de Seleção de Medicamentos Antitumorais , Dispositivos Lab-On-A-Chip , Zeolitas/química , Limite de Detecção , ImidazóisRESUMO
The exploration of novel multivariate heterostructures has emerged as a pivotal strategy for developing high-performance electromagnetic wave (EMW) absorption materials. However, the loss mechanism in traditional heterostructures is relatively simple, guided by empirical observations, and is not monotonous. In this work, we presented a novel semiconductor-semiconductor-metal heterostructure system, Mo-MXene/Mo-metal sulfides (metal = Sn, Fe, Mn, Co, Ni, Zn, and Cu), including semiconductor junctions and Mott-Schottky junctions. By skillfully combining these distinct functional components (Mo-MXene, MoS2, metal sulfides), we can engineer a multiple heterogeneous interface with superior absorption capabilities, broad effective absorption bandwidths, and ultrathin matching thickness. The successful establishment of semiconductor-semiconductor-metal heterostructures gives rise to a built-in electric field that intensifies electron transfer, as confirmed by density functional theory, which collaborates with multiple dielectric polarization mechanisms to substantially amplify EMW absorption. We detailed a successful synthesis of a series of Mo-MXene/Mo-metal sulfides featuring both semiconductor-semiconductor and semiconductor-metal interfaces. The achievements were most pronounced in Mo-MXene/Mo-Sn sulfide, which achieved remarkable reflection loss values of - 70.6 dB at a matching thickness of only 1.885 mm. Radar cross-section calculations indicate that these MXene/Mo-metal sulfides have tremendous potential in practical military stealth technology. This work marks a departure from conventional component design limitations and presents a novel pathway for the creation of advanced MXene-based composites with potent EMW absorption capabilities.
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Angiogenesis is vital for bone fracture healing and plays a significant role in the fate of orthopedic implants. The growth and maintenance of new blood vessels at the fracture site of patients is essential, which promotes the clinical outcome of plasma sprayed Ti (PST) coated orthopedic implants. In order to endow the PST coating with pro-angiogenic effects, deferoxamine-loaded chitosan-based hydrogel was fabricated on the coating surface. Polydopamine-modified chitosan (CS/PDA) hydrogel exhibited enhanced bonding strength to PST coatings as evidenced by scratch test. The deferoxamine-loaded CS/PDA (CS/PDA-DFO) exhibited a sustained drug-release property, and the cumulative concentration of released DFO reached 20.21 µg/mL on day 7. PST-CS/PDA with higher wettability and active group quantity enhanced the viability and adhesion characteristics of human umbilical vein endothelial cells (HUVECs) and upregulated the secretion level of nitric oxide and vascular endothelial growth factor. Moreover, the introduction of DFO in PST-CS/PDA further enhanced the pro-angiogenic effects. Above all, this study offers a novel approach for developing hydrogel coating on orthopedic implants showing enhanced bonding strength and pro-angiogenic effects.
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Timely detection of early-stage cancer holds immense potential in enhancing prognostic outcomes. There is an increasing desire for versatile tools to enable simple, sensitive, and cost-effective cancer detection. By exploiting the extraintestinal metabolic inertness and efficiency renal clearance of sucrose, we designed a liposome nanosensor using sucrose as a messenger to convert tumor-specific esterase activity into glucose meter readout, enabling economical and sensitive urinalysis for cancer detection in point-of-care testing (POCT). Our results demonstrate that the nanosensors exhibited significant signal differences between tumor-bearing and healthy mice in both orthotopic and metastatic tumor models. Additionally, efficient elimination of the nanosensors through the hepatobiliary pathway was observed with no significant toxicity. Such a non-invasive diagnostic modality significantly assists in personalized pharmacological treatment and follow-up efficacy assessment. We envision that this modular liposome nanosensor platform might be applied for economically detecting diverse diseases via a simple urinary test.
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Lipossomos , Sacarose , Lipossomos/química , Animais , Camundongos , Sacarose/química , Sacarose/urina , Humanos , Técnicas Biossensoriais , Neoplasias/diagnóstico , Glucose/análise , Glucose/metabolismo , UrináliseRESUMO
Machining special microstructures on the surface of silicon nitride ceramics helps improve their service performance. However, the high brittleness and low fracture toughness of silicon nitride ceramics make it extremely difficult to machine microstructures on their surface. In this study, a femtosecond laser is used to machine parallel grooved microstructures on the surface of silicon nitride ceramics. The effects of the laser polarization angle, laser single pulse energy, scanning line spacing, and laser scan numbers on the surface morphology and geometric characteristics of grooved microstructures are researched. It is found that a greater angle between the direction of the scanning path and laser polarization is helpful to obtain a smoother surface. As the single pulse energy increases, debris and irregular surface structures will emerge. Increasing the laser scan line spacing leads to clearer and more defined parallel grooved microstructures. The groove depth increases with the increase in the scan numbers. However, when a certain number of scans is reached, the depth will not increase further. This study serves as a valuable research foundation for the femtosecond laser processing of silicon nitride ceramic materials.
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Cuproptosis has drawn enormous attention in antitumor material fields; however, the responsive activation of cuproptosis against tumors using nanomaterials with high atom utilization is still challenging. Herein, a copper-based nanoplatform consisting of acid-degradable copper hydride (CuH) nanoparticles was developed via a microfluidic synthesis. After coating with tumor-targeting hyaluronic acid (HA), the nanoplatform denoted as HA-CuH-PVP (HCP) shows conspicuous damage toward tumor cells by generating Cu+ and hydrogen (H2) simultaneously. Cu+ can induce apoptosis by relying on Fenton-like reactions and lead to cuproptosis by causing mitochondrial protein aggregation. Besides, the existence of H2 can enhance both cell death types by causing mitochondrial dysfunction and intracellular redox homeostatic disorders. In vivo experimental results further exhibit the desirable potential of HCP for killing tumor cells and inhibiting lung metastases, which will broaden the horizons of designing copper-based materials triggering apoptosis and cuproptosis for better antitumor efficacy.
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Cobre , Nanopartículas , Microfluídica , Apoptose , Ácido Hialurônico , HidrogênioRESUMO
Tumor whole cell, carrying a complete set of tumor-associated antigens and tumor-specific antigens, has shown great potential in the construction of tumor vaccines but is hindered by the complex engineering means and limited efficacy to cause immunity. Herein, we provided a strategy for the self-mineralization of autologous tumor cells with palladium ions in microfluidic droplets, which endowed the engineered cells with both immune and catalytic functions, to establish a bioorthogonally catalytic tumor whole-cell vaccine. This vaccine showed strong inhibition both in the occurrence and recurrence of tumor by invoking the immediate antitumor immunity and building a long-term immunity.
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Vacinas Anticâncer , Neoplasias , Humanos , Microfluídica , Imunoterapia , Neoplasias/terapia , Antígenos de NeoplasiasRESUMO
Aside from antibodies, peptides show great potential as immune checkpoint inhibitors (ICIs) due to several advantages, such as better tumor penetration and lower cost. Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Here, we found that LAG-3 expression was higher than programmed cell death protein 1 (PD-1) in multiple human cancers by TCGA databases, and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning, which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/MHC-II. Subsequently, d-amino acids were introduced to substitute the N- and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1, which restores T cell function in vitro and inhibits tumor growth in vivo. Further, a bispecific peptide LFOP targeting both PD-1/PD-L1 and LAG-3/FGL1 was designed by conjugating LFP-D1 with PD-1/PD-L1 blocking peptide OPBP-1(8-12), which activates T cell with enhanced proliferation and IFN-γ production. More importantly, LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune response. In conclusion, we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function, and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response.
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BACKGROUND: Targeting the tumor microenvironment (TME) has emerged as a promising strategy in cancer treatment, particularly through the utilization of immune checkpoint blockade (ICB) agents such as PD-1/PD-L1 inhibitors. Despite partial success, the presence of tumor-associated macrophages (TAMs) contributes to an immunosuppressive TME that fosters tumor progression, and diminishes the therapeutic efficacy of ICB. Blockade of the CD47/SIRPα pathway has proven to be an effective intervention, that restores macrophage phagocytosis and yields substantial antitumor effects, especially when combined with PD-1/PD-L1 blockade. Therefore, the identification of small molecules capable of simultaneously blocking CD47/SIRPα and PD-1/PD-L1 interactions has remained imperative. METHODS: SMC18, a small molecule with the capacity of targeting both SIRPα and PD-L1 was obtained using MST. The efficiency of SMC18 in interrupting CD47/SIRPα and PD-1/PD-L1 interactions was tested by the blocking assay. The function of SMC18 in enhancing the activity of macrophages and T cells was tested using phagocytosis assay and co-culture assay. The antitumor effects and mechanisms of SMC18 were investigated in the MC38-bearing mouse model. RESULTS: SMC18, a small molecule that dual-targets both SIRPα and PD-L1 protein, was identified. SMC18 effectively blocked CD47/SIRPα interaction, thereby restoring macrophage phagocytosis, and disrupted PD-1/PD-L1 interactions, thus activating Jurkat cells, as evidenced by increased secretion of IL-2. SMC18 demonstrated substantial inhibition of MC38 tumor growths through promoting the infiltration of CD8+ T and M1-type macrophages into tumor sites, while also priming the function of CD8+ T cells and macrophages. Moreover, SMC18 in combination with radiotherapy (RT) further improved the therapeutic efficacy. CONCLUSION: Our findings suggested that the small molecule compound SMC18, which dual-targets the CD47/SIRPα and PD-1/PD-L1 pathways, could be a candidate for promoting macrophage- and T-cell-mediated phagocytosis and immune responses in cancer immunotherapy.
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Inibidores de Checkpoint Imunológico , Neoplasias , Animais , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1 , Linfócitos T CD8-Positivos , Antígeno CD47/metabolismo , Antígeno B7-H1 , Fagocitose , Imunoterapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Microambiente TumoralRESUMO
BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer globally, and liver metastasis (CRLM) is the primary cause of death. Hence, it is essential to discover novel prognostic biomarkers and therapeutic drugs for CRLM. METHODS: This study developed two liver metastasis-associated prognostic signatures based on differentially expressed genes (DEGs) in CRLM. Additionally, we employed an interpretable deep learning model utilizing drug sensitivity databases to identify potential therapeutic drugs for high-risk CRLM patients. Subsequently, in vitro and in vivo experiments were performed to verify the efficacy of these compounds. RESULTS: These two prognostic models exhibited superior performance compared to previously reported ones. Obatoclax, a BCL-2 inhibitor, showed significant differential responses between high and low risk groups classified by prognostic models, and demonstrated remarkable effectiveness in both Transwell assay and CT26 colorectal liver metastasis mouse model. CONCLUSIONS: This study highlights the significance of developing specialized prognostication approaches and investigating effective therapeutic drugs for patients with CRLM. The application of a deep learning drug response model provides a new drug discovery strategy for translational medicine in precision oncology.
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Neoplasias Colorretais , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Medicina de Precisão , Prognóstico , Neoplasias Hepáticas/genética , Descoberta de Drogas , Neoplasias Colorretais/genéticaRESUMO
Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.
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The immune checkpoint TIGIT/PVR blockade exhibits significant antitumor effects through activation of NK and CD8+ T cell-mediated cytotoxicity. Immune checkpoint blockade (ICB) could induce tumor ferroptosis through IFN-γ released by immune cells, indicating the synergetic effects of ICB with ferroptosis in inhibiting tumor growth. However, the development of TIGIT/PVR inhibitors with ferroptosis-inducing effects has not been explored yet. In this study, the small molecule Hemin that could bind with TIGIT to block TIGIT/PVR interaction was screened by virtual molecular docking and cell-based blocking assay. Hemin could effectively restore the IL-2 secretion from Jurkat-hTIGIT cells. Hemin reinvigorated the function of CD8+ T cells to secrete IFN-γ and the elevated IFN-γ could synergize with Hemin to induce ferroptosis in tumor cells. Hemin inhibited tumor growth by boosting CD8+ T cell immune response and inducing ferroptosis in CT26 tumor model. More importantly, Hemin in combination with PD-1/PD-L1 blockade exhibited more effective antitumor efficacy in anti-PD-1 resistant B16 tumor model. In summary, our finding indicated that Hemin blocked TIGIT/PVR interaction and induced tumor cell ferroptosis, which provided a new therapeutic strategy to combine immunotherapy and ferroptosis for cancer treatment.
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Ferroptose , Hemina , Imunoterapia , Receptores Imunológicos , Hemina/farmacologia , Receptores Imunológicos/metabolismo , Animais , Humanos , Ferroptose/efeitos dos fármacos , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/terapia , Simulação de Acoplamento Molecular , Células Jurkat , Camundongos Endogâmicos C57BL , Inibidores de Checkpoint Imunológico/farmacologia , Sinergismo Farmacológico , Interferon gama/metabolismo , Interferon gama/imunologia , Receptores Virais/metabolismo , Camundongos Endogâmicos BALB CRESUMO
Oral administration of probiotics orchestrates the balance between intestinal microbes and the immune response. However, effective delivery and in situ colonization are limited by the harsh environment of the gastrointestinal tract. Herein, we provide a microfluidics-derived encapsulation strategy to address this problem. A novel synergistic delivery system composed of EcN Nissle 1917 and prebiotics, including alginate sodium and inulin gel, for treating inflammatory bowel disease and colitis-associated colorectal cancer is proposed. We demonstrated that EcN@AN microparticles yielded promising gastrointestinal resistance for on-demand probiotic delivery and colon-retentive capability. EcN@AN microparticles efficiently ameliorated intestinal inflammation and modulated the gut microbiome in experimental colitis. Moreover, the prebiotic composition of EcN@AN enhanced the fermentation of relative short-chain fatty acid metabolites, a kind of postbiotics, to exert anti-inflammatory and tumor-suppressive effects in murine models. This microfluidcis-based approach for the coordinated delivery of probiotics and prebiotics may have broad implications for gastrointestinal bacteriotherapy applications.