Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(11), P. 6007 - 6023

Published: March 7, 2023

Pyroptosis refers to the process of gasdermin-mediated lytic programmed cell death (PCD) characterized by release pro-inflammatory cytokines. Our knowledge pyroptosis has expanded beyond cellular level and now includes extracellular responses. In recent years, attracted considerable attention due its potential induce host immunity. For instance, at 2022 International Medicinal Chemistry Natural Active Ligand Metal-Based Drugs (MCNALMD) conference, numerous researchers demonstrated an interest in photon-controlled activation ("PhotoPyro"), emerging pyroptosis-engineered approach for activating systemic immunity via photoirradiation. Given this enthusiasm, we share Perspective our views on area expound how why "PhotoPyro" could trigger antitumor (i.e., turning so-called "cold" tumors "hot"). doing so, have tried highlight cutting-edge breakthroughs PhotoPyro while suggesting areas future contributions. By providing insights into current state art serving as a resource individuals interested working area, it is hoped that will set stage evolve broadly applicable cancer treatment strategy.

Language: Английский

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Sodium Bicarbonate Nanoparticles for Amplified Cancer Immunotherapy by Inducing Pyroptosis and Regulating Lactic Acid Metabolism

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(40)

Published: Aug. 17, 2023

Abstract Although immunotherapy has a broad clinical application prospect, it is still hindered by low immune responses and immunosuppressive tumor microenvironment. Herein, simple drug‐free inorganic nanomaterial, alkalescent sodium bicarbonate nanoparticles (NaHCO 3 NPs), prepared via fast microemulsion method for amplified cancer immunotherapy. The obtained NaHCO regulates lactic acid metabolism through acid‐base neutralization so as to reverse the mildly acidic environment. Additionally, can further release high amounts of Na + ions inside cells induce surge in intracellular osmolarity, thus activate pyroptosis pathway immunogenic cell death (ICD), damage‐associated molecular patterns (DAMPs) inflammatory factors, improve responses. Collectively, NPs observably inhibit primary/distal growth metastasis remitted immunosuppression induced activation, showing an enhanced antitumor immunity efficiency. This work provides new paradigm mediated treatment, which potential

Language: Английский

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Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance

Advanced Science, Journal Year: 2023, Volume and Issue: 10(26)

Published: July 12, 2023

In recent years, the incidence of gastrointestinal cancers is increasing, particularly in younger population. Effective treatment crucial for improving patients' survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role growth and development organisms. It also critical maintaining tissue organ homeostasis takes part multiple pathological processes. addition to apoptosis, there are other types programmed such as ferroptosis, necroptosis, pyroptosis, which can induce severe inflammatory responses. Notably, besides pyroptosis contribute occurrence cancers. This review aims provide comprehensive summary on biological roles molecular mechanisms well their regulators hope open up new paths tumor targeted therapy near future.

Language: Английский

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Programmed Targeting Pyruvate Metabolism Therapy Amplified Single‐Atom Nanozyme‐Activated Pyroptosis for Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(24)

Published: Feb. 7, 2024

Abstract Increasing cellular immunogenicity and reshaping the immune tumor microenvironment (TME) are crucial for antitumor immunotherapy. Herein, this work develops a novel single‐atom nanozyme pyroptosis initiator: UK5099 pyruvate oxidase (POx)‐co‐loaded Cu‐NS (Cu‐NS@UK@POx), that not only trigger through cascade biocatalysis to boost of cells, but also remodel immunosuppressive TME by targeting metabolism. By replacing N with weakly electronegative S, original spatial symmetry Cu‐N 4 electron distribution is changed enzyme‐catalyzed process effectively regulated. Compared spatially symmetric nanozymes (Cu‐N SA), S‐doped asymmetric (Cu‐NS SA) exhibit stronger activities, including peroxidase (POD), nicotinamide adenine dinucleotide (NADH) (NOx), L ‐cysteine (LCO), glutathione (GSHOx), which can cause enough reactive oxygen species (ROS) storms pyroptosis. Moreover, synergistic effect SA, UK5099, POx target metabolism, improves increases degree This study provides two‐pronged treatment strategy significantly activate immunotherapy effects via ROS storms, NADH/glutathione/ consumption, oxidation, lactic acid (LA)/ATP depletion, triggering regulating broad vision expanding

Language: Английский

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Oxygen‐carrying semiconducting polymer nanoprodrugs induce sono‐pyroptosis for deep‐tissue tumor treatment

Exploration, Journal Year: 2024, Volume and Issue: 4(4)

Published: Feb. 19, 2024

Abstract Sonodynamic therapy (SDT) has been explored for cancer therapy, especially deep tumors due to its low tissue penetration restriction. The therapeutic efficacy of SDT is limited the complicated tumor microenvironment. This study reports construction oxygen‐carrying semiconducting polymer nanoprodrugs (OSPN pro ) treatment via combining amplified with pyroptosis. An oxygen carrier perfluorohexane, sonodynamic as sonosensitizer, and reactive species (ROS)‐responsive prodrug are co‐loaded into a nanoparticle system, leading formation these nanoprodrugs. Such OSPN show an effective accumulation in tissues after systemic administration, which they deliver relieve hypoxia microenvironment thus mediate producing ROS under ultrasound (US) irradiation, even when covered 2‐cm chicken breast tissue. In addition, ROS‐responsive prodrugs activated by generated trigger pyroptosis cells. sono‐pyroptosis induces strong antitumor immunity obviously higher level infiltrations effector immune cells tumors. Therefore, ‐based combinational can greatly inhibit growth tissue‐covered suppress metastasis. offers nanoplatform strategy.

Language: Английский

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Dual‐Responsive Supramolecular Polymeric Nanomedicine for Self‐Cascade Amplified Cancer Immunotherapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(20)

Published: March 17, 2024

Abstract Insufficient tumor immunogenicity and immune escape from tumors remain common problems in all immunotherapies. Recent studies have shown that pyroptosis, a form of programmed cell death is accompanied by checkpoint inhibitors, can induce effective immunogenic long‐term activation. Therapeutic strategies to jointly pyroptosis reverse immunosuppressive microenvironments are promising for cancer immunotherapy. In this regard, dual‐responsive supramolecular polymeric nanomedicine (NCSNPs) self‐cascade amplify the benefits immunotherapy designed. The NCSNPs formulated β‐cyclodextrin coupling nitric oxide (NO) donor, activator, NLG919, an indoleamine 2,3‐dioxygenase (IDO) inhibitor, self‐assembled through host–guest molecular recognition hydrophobic interaction obtain nanoparticles. possess excellent accumulation bioavailability attributed ingenious engineering. study not only confirms occurrence NO‐triggered first time but also reverses microenvironment sites via IDO inhibitor enhancing infiltration cytotoxic T lymphocytes, achieve remarkable inhibition proliferation. Thus, provides novel strategy

Language: Английский

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Metal–Organic Framework-Based Nanovaccine for Relieving Immunosuppressive Tumors via Hindering Efferocytosis of Macrophages and Promoting Pyroptosis and Cuproptosis of Cancer Cells

ACS Nano, Journal Year: 2024, Volume and Issue: 18(19), P. 12386 - 12400

Published: May 3, 2024

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability produce effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal–organic framework in situ-generate therapeutic vaccination. Once inside early endosome, alkaline overexpressed cells' membrane activates situ type I photodynamic effect of Cu-THBQ/AX for generating •O2–, catalyzes O2 H2O2 •O2– •OH via semiquinone radical catalysis Fenton-like reactions. This surge ROS endosomes triggers caspase-3-mediated proinflammatory pyroptosis activating phospholipase C. Meanwhile, can also induce oligomerization dihydrolipoamide S-acetyltransferase trigger cell cuproptosis. The production could release effectively inhibiting efferocytosis macrophages convert apoptosis cells into secondary necrosis. simultaneous induction pyroptosis, cuproptosis, necrosis converts from "cold" "hot" conditions, making it antigen pool. transformation successfully antitumor response, growth metastasis.

Language: Английский

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A Mitochondria‐Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR‐II Fluorescence/Photoacoustic Imaging‐Guided Phototherapy

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation photosensitizers (PSs), many PSs lack specific subcellular targets are limited to first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy essential for strategies. Here, we synthesized four molecules with varying benzene ring numbers thiopyrylium structures preliminarily explore their properties. The near-infrared-II (NIR-II) PS Z1, higher count, exhibited superior ROS generation mitochondria-targeting abilities, large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high (especially type-I ROS) upon 808 nm laser irradiation, leading efficient mitochondria dysfunction combined apoptosis. Moreover, they exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) photoacoustic (PAI). Furthermore, NPs-mediated effectively inhibited growth minimal adverse effects. Our findings offer promising strategy therapy, warranting further preclinical investigations PDT.

Language: Английский

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Nanomedicine‐Enabled/Augmented Cell Pyroptosis for Efficient Tumor Nanotherapy

Advanced Science, Journal Year: 2022, Volume and Issue: 9(35)

Published: Oct. 20, 2022

The terrible morbidity and mortality of malignant tumors urgently require innovative therapeutics, especially for apoptosis-resistant tumors. Pyroptosis, a pro-inflammatory form programmed cell death (PCD), is featured with pore formation in plasma membrane, swelling giant bubbles, leakage cytoplasmic cytokines, which can remodel the tumor immune microenvironment by stimulating "cold" to be an immunogenic "hot" microenvironment, consequently augment therapeutic efficiency Benefiting from current advances nanotechnology, nanomedicine extensively applied potentiate, enable, pyroptosis enhancing cancer-therapeutic efficacy specificity. This review provides concentrated summary discussion most recent progress achieved this emerging field, highlighting nanomedicine-enabled/augmented specific strategy favoring construction next-generation nanomedicines efficiently induce PCD. It highly expected that further clinical translation accelerated inducing pyroptotic based on bioactive nanomedicines.

Language: Английский

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Bioinspired Multifunctional Silver Nanoparticles for Optical Sensing Applications: A Sustainable Approach

ACS Applied Bio Materials, Journal Year: 2023, Volume and Issue: 6(11), P. 4549 - 4571

Published: Oct. 18, 2023

Silver nanoparticles developed via biosynthesis are the most fascinating nanosized particles and encompassed with excellent physicochemical properties. The bioinspired different shapes sizes have attracted huge attention due to their stability, low cost, environmental friendliness, use of less hazardous chemicals. This is an ideal method for synthesizing a range metal from plants biomolecules. Optical biosensors progressively being fabricated attainment sustainability by using opportunities offered nanotechnology. review focuses mainly on tuning optical properties sensing explore importance applications silver nanoparticles. Further, this deliberates role (Ag NPs) in biomedical, agricultural, environmental, energy applications. Profound insight into antimicrobial these also appreciated. Tailor-made effectuating characteristics can unsurprisingly target tumor cells distribute enwrapped payloads intensively. Existing challenges prospects Ag NPs summarized. expected deliver perceptions about progress next generation outstanding performances various fields promoting sustainable practices fabricating devices.

Language: Английский

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