Ferrous fluoride nanoinitiators reprogram tumor stemness to empower ultrasound-augmented pyroptosis for potent catalytic immunotherapy.

Pyroptosis, a pro-inflammatory programmed cell death mechanism, plays a pivotal role in immune activation. While ultrasound (US)-enhanced catalytic therapy can trigger pyroptosis through increased oxidative stress, tumor cells frequently circumvent this process via intrinsic resistance mechanisms. Herein, ferrous fluoride (FeF) nanoinitiators were developed to promote US-enhanced catalytic activity via stemness reprogramming to amplify pyroptosis-driven antitumor immunity.

Lactate-Modulating Nanoreactors Facilitate Self-Amplifying Pyroptosis and the cGAS-STING Cascade for Potentiated Catalytic-Immunotherapy.

The strategic induction of pyroptosis, coupled with the targeted potentiation of cGAS-STING activation, represents a promising immunostimulatory approach. Herein, an intelligent lactate-depleting LOCoF nanoreactor system is developed that orchestrated self-amplifying pyroptosis induction and cGAS-STING signaling potentiation for enhanced catalytic immunotherapy. This nanoplatform integrated cobalt fluoride (CoF) nanoparticles with lactate oxidase (LOx), endowing it with dual enzymatic capabilities.

Metabolic modulation-driven self-reinforcing pyroptosis-STING nanoadjuvant for potentiated metalloimmunotherapy.

Pyroptosis is a critical process that triggers inflammatory responses and mitochondrial DNA (mtDNA) release, thereby activating the cGAS-STING pathway. However, tumor metabolism, particularly glycolysis, often suppresses immune activation. To address this, we developed GOCoF, a self-amplifying pyroptosis-STING nanoadjuvant that integrates glucose oxidase (GOx) with cobalt fluoride (CoF) nanoenzymes.

Engineered Nano-Micro Pyroptosis Generators: A Magnetic-Metallo-Immunotherapeutic Strategy to Reinforce Transarterial Embolization.

Gasdermin-mediated pyroptosis represents a promising immunotherapeutic strategy, yet requires precise tumor-specific activation. Magnetic hyperthermia therapy (MHT) has the potential to induce pyroptosis in hepatocellular carcinoma (HCC), while its efficacy is limited by suboptimal heating efficiency and tumor resistance. Herein, we developed an innovative magnetic-metallo-immunotherapeutic platform by engineering nanomicro pyroptosis generators, thereby enhancing transarterial embolization (TAE).

Magnesium microspheres for enhanced transarterial chemoembolization therapy of hepatocellular carcinoma: From animal models to a pilot clinical study.

Transarterial chemoembolization (TACE) has been extensively used in clinic to treat unresectable hepatocellular carcinoma (HCC). Herein, magnesium microspheres (Mg MSs) were used as embolic devices to enhance lipiodol-mediated TACE. After being dispersed in lipiodol and injected into tumors, Mg MSs would continuously generate hydrogen and magnesium hydroxide, which could neutralize the acidic tumor microenvironment, restore exhausted CD8 T cells, reverse immunosuppression, and trigger specific T cell-mediated antitumor responses, synergistically resulting in inhibited tumor growth.

Dually fluorinated unimolecular micelles for stable oxygen-carrying and enhanced photosensitive efficiency to boost photodynamic therapy against hypoxic tumors.

Tumor hypoxia is one of key challenges in deep tumor photodynamic therapy (PDT), and how to fix this issue is attracting ongoing concerns worldwide. This work demonstrates dually fluorinated unimolecular micelles with desirable and stable oxygen-carrying capacity, high cellular penetration, and integrative type I & II PDT for deep hypoxic tumors. Dually fluorinated star copolymers with fluorinated phthalocyanines as the core are prepared through photoinitiated electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization under irradiation with NIR LED light at room temperature, followed by assembly into unimolecular micelles.

Manganese Galvanic Cells Intervene in Tumor Metabolism to Reinforce cGAS-STING Activation for Bidirectional Synergistic Hydrogen-Immunotherapy.

The cGAS-STING pathway is pivotal in initiating antitumor immunity. However, tumor metabolism, particularly glycolysis, negatively regulates the activation of the cGAS-STING pathway. Herein, Mn galvanic cells (MnG) are prepared via liquid-phase exfoliation and in situ galvanic replacement to modulate tumor metabolism, thereby enhancing cGAS-STING activation for bidirectional synergistic H-immunotherapy.

Microbial and Transcriptomic Landscape Associated With Neutrophil Extracellular Traps in Perianal Fistulizing Crohn's Disease.

Background: Perianal fistulizing Crohn's disease (pfCD) poses significant healing challenges, closely associated with neutrophil extracellular traps (NETs). This study aimed to investigate the microbe-host interactions influencing NETs in pfCD.

Methods: From January 2019 to July 2022, patients with pfCD were screened at Ren Ji Hospital.

Antimony Component Schottky Nanoheterojunctions as Ultrasound-Heightened Pyroptosis Initiators for Sonocatalytic Immunotherapy.

Pyroptosis, an inflammatory modality of programmed cell death associated with the immune response, can be initiated by bioactive ions and reactive oxygen species (ROS). However, bioactive ion-induced pyroptosis lacks specificity, and further exploration of other ions that can induce pyroptosis in cancer cells is needed. Sonocatalytic therapy (SCT) holds promise due to its exceptional penetration depth; however, the rapid recombination of electron-hole (e-h) pairs and the complex tumor microenvironment (TME) impede its broader application.

Magnesium implants with alternating magnetic field-enhanced hydrogen release and proton depletion for anti-infection treatment and tissue repair.

Implant-related osteomyelitis is a formidable hurdle in the clinical setting and is characterized by inflammation, infection, and consequential bone destruction. Therefore, effective reactive oxygen species (ROS) scavenging, bacterial killing, and subsequent bone tissue repair are urgently needed for the treatment of difficult-to-heal osteomyelitis. Herein, we utilized the eddy-thermal effect of magnesium (Mg) implants under an alternating magnetic field (AMF) for the controlled release of H gas and ions (OH and Mg) for the treatment of osteomyelitis.

Oncolytic mineralized bacteria as potent locally administered immunotherapeutics.

Oncolytic bacteria can trigger innate immune activity. However, the antitumour efficacy of inactivated bacteria is poor, and attenuated live bacteria pose substantial safety risks. Here we show that intratumourally injected paraformaldehyde-fixed bacteria coated with manganese dioxide potently activate innate immune activity, modulate the immunosuppressive tumour microenvironment and trigger tumour-specific immune responses and abscopal antitumour responses.

Thymopentin ameliorates experimental colitis via inhibiting neutrophil extracellular traps.

Background: The long-term prognosis of Crohn's disease (CD) remains unsatisfactory. Therefore, we assessed the therapeutic effect of thymopentin (TP5) in a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, which mimics CD, and analyzed its impact on neutrophil extracellular traps (NETs).

Methods: NET markers, including myeloperoxidase (MPO), neutrophil elastase (NE), citrullinated histone H3 (CitH3), peptidyl arginine deiminase IV (PAD4), and double-stranded DNA (dsDNA) were assessed by immunostaining and enzyme-linked immunosorbent assay.

Bioactive Vanadium Disulfide Nanostructure with "Dual" Antitumor Effects of Vanadate and Gas for Immune-Checkpoint Blockade-Enhanced Cancer Immunotherapy.

Bioactive inorganic nanomaterials and the biological effects of metal ions have attracted extensive attention in tumor therapy in recent years. Vanadium (V), as a typical bioactive metal element, regulates a variety of biological functions. However, its role in antitumor therapy remains to be revealed.

Manganese molybdate nanodots with dual amplification of STING activation for "cycle" treatment of metalloimmunotherapy.

Certain types of cationic metal ions, such as Mn are able to activate immune functions via the stimulator of interferon genes (STING) pathway, showing potential applications in eliciting antitumor immunity. How anionic ions interact with immune cells remains largely unknown. Herein, selecting from a range of cationic and anionic ions, we were excited to discover that MoO could act as a cGAS-STING agonist and further confirmed the capability of Mn to activate the cGAS-STING pathway.

Liquid metal microspheres with an eddy-thermal effect for magnetic hyperthermia-enhanced cancer embolization-immunotherapy.

Patients with hepatocellular carcinoma (HCC) display poor prognosis because HCC involves a high rate of metastasis and regrowth. Herein, we present an effective strategy to treat HCC using magnetic hyperthermia therapy (MHT)-enhanced cancer immunotherapy combined with transcatheter arterial embolization (TAE). Uniform liquid metal microspheres (LM MSs) obtained by microfluidic technology with powerful eddy-thermal effects could be used as both MHT and TAE agents for effective cancer therapy.

Nonferrous Ferroptosis Inducer Manganese Molybdate Nanoparticles to Enhance Tumor Immunotherapy.

Tumor immunotherapy is an important tool in oncology treatment. However, only a small percentage of patients have an effective immune response to tumor immunotherapy due to the poor infiltration of pro-inflammatory immune cells in immune "cold" tumors and an immunosuppressive network in the tumor microenvironment (TME). Ferroptosis has been widely used as a novel strategy to enhance tumor immunotherapy.

Rational Design of Biomaterials to Potentiate Cancer Thermal Therapy.

Cancer thermal therapy, also known as hyperthermia therapy, has long been exploited to eradicate mass lesions that are now defined as cancer. With the development of corresponding technologies and equipment, local hyperthermia therapies such as radiofrequency ablation, microwave ablation, and high-intensity focused ultrasound, have has been validated to effectively ablate tumors in modern clinical practice. However, they still face many shortcomings, including nonspecific damages to adjacent normal tissues and incomplete ablation particularly for large tumors, restricting their wide clinical usage.

Oral Delivery of Therapeutic Antibodies with a Transmucosal Polymeric Carrier.

Therapeutic proteins are playing increasingly important roles in treating numerous types of diseases. However, oral administration of proteins, especially large ones (e.g.

The combination of eddy thermal effect of biodegradable magnesium with immune checkpoint blockade shows enhanced efficacy against osteosarcoma.

Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS.

Magnetic Targeting Nanocarriers Combined with Focusing Ultrasound for Enhanced Intracerebral Hemorrhage Therapy.

Intracerebral hemorrhage (ICH) remains a significant cause of morbidity and mortality around the world, and surgery is still the most direct and effective way to remove ICH. However, the potential risks brought by surgery, such as normal brain tissue damage, post-operative infection, and difficulty in removing deep hematoma, are still the main problems in the surgical treatment of ICH. Activation of the peroxisome proliferator-activated receptor gamma (PPARγ) is reported to show a good therapeutic effect in hematoma clearance.

Oxygen-Deficient Molybdenum Oxide Nanosensitizers for Ultrasound-Enhanced Cancer Metalloimmunotherapy.

Oxygen-deficient molybdenum oxide (MoO ) nanomaterials are prepared as novel nanosensitizers and TME-stimulants for ultrasound (US)-enhanced cancer metalloimmunotherapy. After PEGylation, MoO -PEG exhibits efficient capability for US-triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoO -PEG generates a massive amount of ROS to induce cancer cell damage and immunogenic cell death (ICD), which can effectively suppress tumor growth.

Calcium Hydride-Based Dressing to Promote Wound Healing.

Wound microenvironment with excess reactive oxygen species (ROS) can significantly inhibit wound healing. Encouraged by hydrogen molecules (H ) with effective ROS scavenging and calcium hydride (CaH ) with sufficient H supply, the authors for the first time employed CaH as a therapeutic H donor and starch as a diluent to construct CaH pulvis dressing for wound healing treatment. It has been found that CaH by generating H exhibited excellent ROS scavenging performance, favorable for preserving the oxidative-stress-induced cell death.