Self-Cascaded Pyroptosis-STING Initiators for Catalytic Metalloimmunotherapy

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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

Язык: Английский

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Tumor Microenvironment‐Driven Structural Transformation of Vanadium‐Based MXenzymes to Amplify Oxidative Stress for Multimodal Tumor Therapy

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

MXenzymes, a promising class of catalytic therapeutic material, offer great potential for tumor treatment, but they encounter significant obstacles due to suboptimal efficiency and kinetics in the microenvironment (TME). Herein, this study draws inspiration from electronic structure transition metal vanadium, proposing leverage TME specific-features induce structural transformations sheet-like vanadium carbide MXenzymes (TVMz). These trigger cascading reactions that amplify oxidative stress, thereby significantly enhancing multimodal therapy. Specifically, engineered HTVMz, coated with hyaluronic acid, exhibits good stability generates thermal effect under NIR-II laser irradiation. The effect, combined characteristics, facilities transformation into ultra-small oxide nanozymes (VOx). enlarged surface area VOx substantially enhances ROS regeneration amplifies which promotes lysosomal permeability induces endoplasmic reticulum stress. high-valent interacts intracellular glutathione, disrupting redox homeostasis intensifying stress further. amplifications accelerate apoptosis, ferroptosis, suppress HSP90 expression. Consequently, heightened sensitivity HTVMz synergistically cell death via pathways. This presents an innovative strategy therapy by manipulating structures, advancing field

Язык: Английский

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Dual Enzyme-Driven Cascade Reactions Modulate Immunosuppressive Tumor Microenvironment for Catalytic Therapy and Immune Activation

ACS Nano, Год журнала: 2024, Номер 18(44), С. 30345 - 30359

Опубликована: Окт. 21, 2024

Lactate-enriched tumor microenvironment (TME) fosters an immunosuppressive milieu to hamper the functionality of tumor-associated macrophages (TAMs). However, tackling effects wrought by lactate accumulation is still a big challenge. Herein, we construct dual enzyme-driven cascade reaction platform (ILH) with TME modulation for photoacoustic (PA) imaging-guided catalytic therapy and immune activation. The ILH composed iridium (Ir) metallene nanozyme, oxidase (LOx), hyaluronic acid (HA). combination Ir nanozyme LOx can not only efficiently consume reverse into immunoreactive one promoting polarization TAMs from M2 M1 phenotype, thus enhancing antitumor defense, but also alleviate hypoxia as well induce strong oxidative stress, triggering immunogenic cell death (ICD) activating immunity. Furthermore, photothermal performance strengthen ability endow PA response. Based on changes in signals endogenous molecules, three-dimensional multispectral imaging was utilized track process vivo. This work provides nanoplatform activation regulating TME.

Язык: Английский

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Tumor microenvironment–responsive and modulatory manganese-based nanoenzyme for enhanced tumor immunotherapy

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 3, 2025

The characteristics of the tumor microenvironment (TME) have a close and internal correlation with effect cancer immunotherapy, significantly affecting progression metastasis cancer. rational design nanoenzymes that possess ability to respond regulate TME is driving new direction in catalytic immunotherapy. In this study, we designed multifunctional manganese (Mn)-based nanoenzyme responsive acidic pH overxpressed H2O2 at site holds capability modulating hypoxic immunosuppressive for synergistic anti-tumor photothermal/photodynamic/immunotherapy. We found artificial promoted peroxidase-like catalase-like activities catalyzed in-situ decomposition H2O2, metabolic waste product TME, into ∙OH O2, resulting ROS burst killing tumors relieving enhance therapy. Besides photothermal enhancement burst-induced immunogenic cell death, combination Mn2+ released from Mn-based programmed death-ligand 1 blockade triggered significant immune response. A remarkable vivo therapeutic was achieved effective inhibition primary growth lung metastasis. Therefore, TME-responsive offers safe efficient platform reversing achieving

Язык: Английский

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Rational Design of Single‐Atom Nanozymes for Combination Cancer Immunotherapy

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Abstract Remodeling of the tumor immune microenvironment and enhancement antitumor responses are necessary to overcome immunotherapy resistance in tumors. However, heterogeneity complexity evasion mechanisms pose significant therapeutic challenges. Nanozymes exhibit enzyme‐like characteristics unique nanomaterial properties, showing potential for therapy. design effective nanozymes remains complex, inefficient, functionally limited. Therefore, this study, a novel strategy combining rationally designed single‐atom (SAzymes) with checkpoint blockade (ICB) therapy is established. Molybdenum SAzymes supported on graphitic carbon nitride (Mo SAs) constructed using 25 transition metal candidates from 4th 6th periods based high‐throughput calculations optimal piezoelectric‐enhanced multienzyme‐like activities. Upon activation by ultrasound, Mo SAs exerted potent effects against ICB‐resistant tumors remodeled inducing immunogenic cell death, alleviating hypoxia, modulating chemokine expression Combination anti‐programmed death protein‐1 antibodies further enhanced their efficacy, highlighting treat

Язык: Английский

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Dual-Driven Selenium Janus Single-Atom Nanomotors for Autonomous Regulating Mitochondrial Oxygen Imbalance to Catalytic Therapy of Rheumatoid Arthritis

Redox Biology, Год журнала: 2025, Номер 81, С. 103574 - 103574

Опубликована: Март 1, 2025

O2 deficiency and excessive reactive oxygen nitrogen species (RONS) in macrophage mitochondria is a key factor causing imbalance rheumatoid arthritis microenvironment (RAM). Although nanocatalytic therapy that simultaneously produce eliminate RONS offer novel strategy for RA therapy, the therapeutic efficacy of nanozymes limited by lack autonomous targeting into mitochondria. Herein, we constructed Janus-structured nanomotor (Pd@MSe) with ability embedding Pd single-atom mesoporous selenium (MSe) nanozymes, obtained composite (Pd@MSe-TPP) dual-driven forces modifying triphenylphosphine (TPP) MSe hemisphere. In RAM, Pd@MSe-TPP achieved autonomously target macrophages driven generation TPP effect, moreover under effect enhanced electronic transfer between which significantly boosted GPx catalytic activity further effectively diffusion nanomotor, thus quickly resorted balance. Additionally, while regulating imbalance, enable rapidly blocked inflammatory cascade, restored mitochondrial function alleviated inflammation, prevented cartilage degradation inhibited progression. Therefore, exquisitely designed nanoplatform to regulation arthritic provides new direction clinical translation nanomedicine.

Язык: Английский

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A Carbon‐Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(26)

Опубликована: Апрель 22, 2024

Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e

Язык: Английский

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Harnessing the Engineered Probiotic‐Nanosystem to Remodulate Tumor Extracellular Matrix and Regulate Tumor‐Colonizing Bacteria for Improving Pancreatic Cancer Chemo‐Immunotherapy

Small, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 24, 2024

Abstract Poor chemotherapy efficacy in pancreatic cancer is attributed to limited drug permeation caused by the dense extracellular matrix (ECM) and degradation induced tumor‐colonizing bacteria. Here, a tumor‐targeting probiotic‐nanosystem elaborately designed remodulate ECM selectively regulate bacteria for improving chemo‐immunotherapy against cancer. Specifically, drug‐loaded liposomes are conjugated with Clostridium Butyricum (CB) via metalloproteinase‐2 (MMP‐2)‐responsive peptide construct probiotic‐nanosystem. Particularly, vactosertib (VAC, transforming growth factor‐β1 receptor inhibitor) delivered silence active stellate cells (PSCs) inhibiting development of ECM, resulting loosened providing golden opportunity deep penetration drugs immune cells. Subsequently, gemcitabine (GEM) efficiently into core tumors probiotic‐nanosystem, achieving an enhanced efficacy. Noteworthily, CB can alleviate γ‐proteobacteria ‐mediated GEM through competitively reducing contents promoting amounts tumor‐inhibiting bacteria, thereby significantly potentiating therapeutic effect GEM. The engineered not only enhance GEM‐induced immunogenic cell death (ICD) tumor activate antitumor responses but also markedly increase tumor‐infiltration effector heighten tumoricidal immunity, offering promising strategy

Язык: Английский

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A Carbon‐Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy

Angewandte Chemie, Год журнала: 2024, Номер 136(26)

Опубликована: Апрель 22, 2024

Abstract Photoimmunotherapy is a promising cancer treatment modality. While potent 1‐e − oxidative species are known to induce immunogenic cell death (ICD), they also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post‐generation radical reinforcement. Namely, non‐oxidative radicals first generated subsequently activated into powerful ICD. Here, we developed photo‐triggered molecular donor ( NPCD565 ) of nitrosoperoxycarbonate (ONOOCO 2 ), the its class our knowledge, further evaluated feasibility for immunotherapy. Upon irradiation light within broad spectral region from ultraviolet red, ONOOCO released along bright rhodamine dye RD565 whose fluorescence reliable convenient build‐in reporter localization, kinetics, dose generation. photolysis in 4T1 cells, damage‐associated patterns (DAMPs) indicative ICD were observed confirmed exhibit immunogenicity induced maturation dendritic cells. In vivo studies bilateral tumor‐bearing mouse model showcased tumor‐killing capability primary tumors growth suppression distant tumors. work unveils , has potential photo‐immunotherapy cancer.

Язык: Английский

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Nanoparticle‐Based drug delivery strategies for targeted therapy to hypoxic solid tumors

Chemical Engineering Journal, Год журнала: 2024, Номер unknown, С. 158081 - 158081

Опубликована: Ноя. 1, 2024

Язык: Английский

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