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

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(11), С. 6007 - 6023

Опубликована: Март 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.

Язык: Английский

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Nanoparticles Synergize Ferroptosis and Cuproptosis to Potentiate Cancer Immunotherapy

Advanced Science, Год журнала: 2024, Номер 11(23)

Опубликована: Март 13, 2024

Abstract The recent discovery of copper‐mediated and mitochondrion‐dependent cuproptosis has aroused strong interest in harnessing this novel mechanism cell death for cancer therapy. Here the design a core‐shell nanoparticle, CuP/Er, co‐delivery copper (Cu) erastin (Er) to cells synergistic ferroptosis is reported. anti‐Warburg effect Er sensitizes tumor Cu‐mediated cuproptosis, leading irreparable mitochondrial damage by depleting glutathione enhancing lipid peroxidation. CuP/Er induces immunogenic death, enhances antigen presentation, upregulates programmed death‐ligand 1 expression. Consequently, promotes proliferation infiltration T cells, when combined with immune checkpoint blockade, effectively reinvigorates mediate regression murine colon adenocarcinoma triple‐negative breast prevent metastasis. This study suggests unique opportunity synergize combination therapy nanoparticles elicit antitumor effects potentiate current immunotherapies.

Язык: Английский

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Mitochondria-targeted photodynamic therapy triggers GSDME-mediated pyroptosis and sensitizes anti-PD-1 therapy in colorectal cancer

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(3), С. e008054 - e008054

Опубликована: Март 1, 2024

Background The effectiveness of immune checkpoint inhibitors in colorectal cancer (CRC) is limited due to the low tumor neoantigen load and infiltration most microsatellite-stable (MSS) tumors. This study aimed develop a mitochondria-targeted photodynamic therapy (PDT) approach provoke host antitumor immunity MSS-CRC elucidate underlying molecular mechanisms. Methods role mechanism PDT inhibiting CRC progression inducing pyroptosis were evaluated both vitro vivo. effects sensitization on PD-1 blockade also assessed CT26 4T1 tumor-bearing mouse models. Results Here, we report that using IR700DX-6T, photosensitizer targeting mitochondrial translocation protein, may trigger an response initiated by CRC. Mechanistically, IR700DX-6T-PDT produced reactive oxygen species light irradiation promoted downstream p38 phosphorylation active caspase3 (CASP3)-mediated cleavage gasdermin E (GSDME), subsequently pyroptosis. Furthermore, enhanced sensitivity cells blockade. Decitabine, demethylation drug used treat hematologic neoplasms, disrupted abnormal methylation pattern GSDME cells, efficacy IR700DX-6T-PDT, elicited potent combination with IR700DX-6T-PDT. Conclusion Our work provides clear understanding immunogenic cell death triggered PDT, offering new for enhancing

Язык: Английский

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Pyroptosis: A road to next-generation cancer immunotherapy

Seminars in Immunology, Год журнала: 2023, Номер 68, С. 101782 - 101782

Опубликована: Июнь 10, 2023

Язык: Английский

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Zinc Coordination Lipid Nanoparticles Co‐Delivering Calcium Peroxide and Chelating STING agonist for Enhanced Cancer Metalloimmunotherapy

Small, Год журнала: 2024, Номер 20(46)

Опубликована: Авг. 8, 2024

Abstract Metalloimmunotherapy has achieved great preclinical success against malignant tumors. Nonetheless, the limited immune cell infiltration and impaired immunogenicity within tumor microenvironment (TME) significantly hinder its translation to clinical applications. In this study, a zinc coordination lipid nanoparticle is developed loaded with calcium peroxide hydrate (CaO 2 ) nanoparticles STING agonist diABZI‐2, which termed A‐CaO ‐Zn‐LNP. The release of Zn 2+ from ‐Zn‐LNP overload synergistically induced immunogenic death (ICD). addition, CaO can consume H + oxygen (O under acidic conditions. This treatment increased pH alleviated hypoxia TME. Along cGAS‐STING activation by ultimately results in enhanced anti‐tumor systemic immunity long‐term memory via alleviating immunosuppressive microenvironment. Taken together, offers new nanoplatform that expands application for cancer metalloimmunotheray.

Язык: Английский

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Apoptosis‐Sensitizing Tumor Nanomedicine by Regulating Pyroptosis‐Associated Inflammatory Cell Death

Advanced Functional Materials, Год журнала: 2024, Номер 34(44)

Опубликована: Май 25, 2024

Abstract The vigorous development of cancer nanomedicine has revolutionized traditional oncology medicine, but it is also limited by the continuous mutation cunning cells, leading to apoptosis insensitivity and therapeutic disappointment. Inflammatory‐regulated cell death (RCD), especially pyroptosis‐related death, demonstrates huge potential for sensitization due its unique biochemical characteristics. aim this research present a thorough synopsis current knowledge on pyroptosis‐associated inflammatory including pyroptosis, cuproptosis, PANoptosis, synergistic function in nano therapy. Paradigm studies death‐mediated apoptosis‐sensitizing tumor nanotherapeutics are introduced detail, coordination mechanisms based nanomaterials discussed. In addition, multi‐angle analysis future prospects pyroptosis‐sensitized various emphasized further expand application scope RCD. It believed that emerging auxiliary treatments RCD will greatly promote progress nanomedicine.

Язык: Английский

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Self-assembled nanodrug based on ferroptosis inducer and sonosensitizer for enhanced sonodynamic-triggered multimodal synergistic therapy of prostate cancer

European Journal of Pharmaceutics and Biopharmaceutics, Год журнала: 2025, Номер 208, С. 114656 - 114656

Опубликована: Фев. 3, 2025

Язык: Английский

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Combination of an LDH-based platform with microRNA for the treatment of myocardial Ischemia-Reperfusion injury by pyroptosis inhibition via the CaSR/PLCγ1/IP3R pathway

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 160833 - 160833

Опубликована: Фев. 1, 2025

Язык: Английский

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Redox-activated photosensitizers for visualizing precise diagnosis and potentiating cancer therapy

Coordination Chemistry Reviews, Год журнала: 2024, Номер 507, С. 215734 - 215734

Опубликована: Март 5, 2024

Язык: Английский

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Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Май 3, 2025

Pyroptosis is a distinct form of programmed cell death characterized by the rupture membrane and robust inflammatory responses. Increasing evidence suggests that pyroptosis significantly affects tumor microenvironment antitumor immunity releasing damage-associated molecular patterns (DAMPs) pro-inflammatory mediators, thereby establishing it as pivotal target in cancer immunotherapy. This review thoroughly explores mechanisms underlying pyroptosis, with particular focus on inflammasome activation gasdermin family proteins (GSDMs). It examines role pyroptotic reshaping immune (TIME) involving both cells, discusses recent advancements targeting pathways through therapeutic strategies such small molecule modulators, engineered nanocarriers, combinatory treatments checkpoint inhibitors. We also advances future directions to enhance immunotherapy inhibitors, adoptive therapy, vaccines. study suggested offers promising avenue amplify responses surmount resistance existing immunotherapies, potentially leading more efficacious treatments.

Язык: Английский

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