Self-Cascaded Pyroptosis-STING Initiators for Catalytic Metalloimmunotherapy

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Gasdermin (GSDM)-mediated pyroptosis involves the induction of mitochondrial damage and subsequent release DNA (mtDNA), which is anticipated to activate cGAS-STING pathway, thereby augmenting antitumor immune response. However, challenges lie in effectively triggering cancer cells subsequently enhancing activation with specificity. Herein, we developed intelligent self-cascaded pyroptosis-STING initiators cobalt fluoride (CoF2) nanocatalysts for catalytic metalloimmunotherapy. CoF2 a semiconductor structure enzyme-like activity generated substantial amount reactive oxygen species (ROS) under stimulation by endogenous H2O2 exogenous ultrasound. Importantly, discovered that Co-based nanomaterials themselves induce cells. Therefore, initially acted as inducers, caspase-1/GSDMD-dependent via Co2+ ROS, leading mtDNA release. Subsequently, were further utilized STING agonists specifically capable detecting pathway. These cascade events triggered robust response, modulating immunosuppressive tumor microenvironment into an immune-supportive state, providing favorable support therapy. This innovative strategy not only significantly impeded growth primary but also elicited response augment efficacy checkpoint inhibitors preventing distant progression. Overall, this study proposed self-cascade activating amplifying pathway specificity mediated pyroptosis, representing valuable avenue future

Language: Английский

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

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Abstract The cGAS‐STING pathway is pivotal in initiating antitumor immunity. However, tumor metabolism, particularly glycolysis, negatively regulates the activation of pathway. Herein, Mn galvanic cells (MnG) are prepared via liquid‐phase exfoliation and situ replacement to modulate thereby enhancing for bidirectional synergistic H 2 ‐immunotherapy. obtained MnG can be etched by water, enabling efficient sustained generation gas 2+ . not only activated amplified through release but also regulated glucose metabolism inhibit expression three prime repair exonuclease (TREX2), synergistically injection into tumors resulted a robust immune response, providing favorable support therapy. Consequently, combination with checkpoint blockade therapy significant suppression both primary distant tumors. Furthermore, MnG‐lipiodol dispersion exhibited remarkable efficacy transarterial embolization (TAE)‐gas‐immunotherapy rabbit orthotopic liver model. present study underscores significance employing metal cell strategy enhanced immunotherapy, offering novel approach rational design bioactive materials augment immunotherapeutic effectiveness.

Language: Английский

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Endoplasmic Reticulum-Targeted Polymer-Manganese Nanocomplexes for Tumor Immunotherapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Manganese ions (Mn2+) are an immune activator that enhances the activation of both cGAS and STING proteins. The signaling subsequential responses predominantly associated with endoplasmic reticulum (ER). Therefore, ER targeting Mn2+ in subcellular compartments would promote pathways. Herein, we report design ER-targeted manganese-based nanocomplexes (NCs) by complexation a zwitterionic polymer, poly[2-(N-oxide-N,N-dimethylamino) ethyl methacrylate] (OPDMA). Mn/OPDMA (Mn/OPDMA NCs) keep long blood circulation for tumor accumulation trigger adsorption-mediated transcytosis extravasation deep penetration. Notably, tumor-associated macrophages, NCs can preferentially translocate to their ERs, significantly enhancing cGAS-STING pathway macrophage polarization IFN-β secretion. In mouse colon hepatocellular cancer models, intravenously administrated efficiently remodel microenvironment, greatly retard growths 2.4- 5-fold, prolong survivals compared free Mn2+-treated mice. This study provides delivery achieves robust and, thus, potent systemic inhibition without toxicity Mn2+.

Language: Английский

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Enhancement of Osseointegration via Endogenous Electric Field by Regulating the Charge Microenvironments around Implants

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

The regulation of the charged microenvironment around implants is an effective way to promote osseointegration. Although homeostasis plays integral role in tissues, current research externally invasive and unsuitable for clinical applications. In this study, functional materials with different surface potential differences are prepared by changing spatial layout Ta Ag on a Ti-6Al-4V alloy (TC4). This naturally formed endogenous electric field (EEF) negatively cell membrane after vivo implantation promoted osseointegration at interface between bone implant through upregulation Ca

Language: Английский

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Double-metal ion adjuvant stabilized Pickering emulsion to amplify humoral and cellular immune responses

Nano Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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HIFU postoperative hypoxia enables metal-organic frameworks amplifying banoxantrone and STING activation for enhanced immunotherapy

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 159704 - 159704

Published: Jan. 1, 2025

Language: Английский

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In Vivo Time-Resolved Single-Cell RNA-Seq Reveals Chemotherapy-Induced Transcriptional Dynamics in Tumor Infiltrating Lymphocytes

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Single-cell RNA sequencing (scRNA-seq) using metabolic labeling enables detailed analysis of dynamic gene expression within single cells. However, most studies are limited to in vitro settings, restricting the exploration vivo transcriptomic dynamics. To address this, we developed scDyna-seq, a time-resolved scRNA-seq method for applications 4-thiouridine (4sU) labeling. scDyna-seq efficiently captures nascent RNA, allowing precise tracking both and contexts, including crossing blood–brain blood-fetal barriers. It is also compatible with other single-cell multiomics approaches. In mouse bladder cancer model, revealed that cisplatin (cis-diaminodichloroplatinum, CDDP) induced significant changes tumor-infiltrating lymphocytes, particularly genes related costimulation, effector functions, exhaustion, which were not detected by conventional methods. When coupled scTCR-seq, showed increased TCR clonal expansion linked CDDP-induced immunogenic death neoantigen production. conclusion, offers safe, as well analysis, expanding our understanding cellular dynamics facilitating research health disease.

Language: Английский

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Translational study of the regulatory mechanism by which immune synapses enhance immune cell function

Cancer Letters, Journal Year: 2025, Volume and Issue: 614, P. 217542 - 217542

Published: Feb. 7, 2025

Language: Английский

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Immunity‐Modulating Metal‐Based Nanomaterials for Cancer Immunotherapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract Cancer immunotherapy, which leverages the body's immune system to combat cancer, offers promise of lower toxicity and higher therapeutic efficacy compared conventional treatments. However, current immunotherapeutic approaches face significant challenges including variable patient response, immune‐related adverse events, high costs, underscoring urgent need for innovative strategies. Metal‐based nanomaterials have emerged as a promising avenue in cancer immunotherapy due their unique physicochemical properties immune‐regulating capabilities. Despite potential, concerns about toxicity, incomplete understanding modulation mechanisms, early‐stage design strategies hinder clinical translation. This review summarizes recent advancements metal‐based elucidates mechanisms by they enhance antitumor immunity responses, explores potential synergistic effects combining multiple metals. We also discuss key future perspectives application, aiming provide theoretical foundation development immunotherapies promote broader application treatment.

Language: Английский

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Manganese-Driven Plasmid Nanofibers Formed In Situ for Cancer Gene Delivery and Metalloimmunotherapy

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

While nucleic-acid-based cancer vaccines hold therapeutic potential, their limited immunogenicity remains a challenge due in part to the low efficiency of cytoplasmic delivery caused by lysosomal entrapment. In this work, we found that plasmids encoding both an antigen and STING agonist protein adjuvant can self-assemble into coordination nanofibers, triggered manganese ions. We developed strategy construct DNA vaccine, termed MnO2-OVA-CDA-mem, formed coencapsulation dioxide (MnO2), antigen-expressing plasmid (encoding ovalbumin, OVA), enzyme-expressing agonist, CDA) within dendritic cell (DC) membranes. Upon uptake acidic lysosomes, Mn2+ released from MnO2 nucleic acids undergo morphological change nanospheres (∼180 nm diameter) nanofibers (∼1 μm length), resulting increase mechanical strength about 9-fold consequently membrane disruption. The OVA adjuvants CDA cytoplasm strong DC activation antigen-specific CD8+ T metalloimmune responses, significantly inhibiting growth B16-OVA tumors inducing long-term immune memory. Altogether, MnO2-OVA-CDA-mem holds potential as platform for acid using situ self-assembly metal-driven, stimulus-responsive, programmable manner metalloimmunotherapy.

Language: Английский

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