Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 2, 2023

Immunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable triggering both ferroptosis remains limited. Here we show construction a covalent organic framework (COF-919) from planar twisted AIEgen-based motifs dual-inducer for efficient Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, longer lifetime to favor generation reactive oxygen species (ROS) photothermal conversion, pyroptosis. Because its good ROS production capability, it upregulates intracellular lipid peroxidation, leading glutathione depletion, low expression peroxidase 4, induction ferroptosis. Additionally, by effectively inhibits tumor metastasis recurrence, resulting in over 90% growth inhibition cure rates exceeding 80%.

Language: Английский

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Genetically Edited Cascade Nanozymes for Cancer Immunotherapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(19), P. 12295 - 12310

Published: May 2, 2024

Immune checkpoint blockade (ICB) has brought tremendous clinical progress, but its therapeutic outcome can be limited due to insufficient activation of dendritic cells (DCs) and infiltration cytotoxic T lymphocytes (CTLs). Evoking immunogenic cell death (ICD) is one promising strategy promote DC maturation elicit T-cell immunity, whereas low levels ICD induction solid tumors restrict durable antitumor efficacy. Herein, we report a genetically edited membrane-coated cascade nanozyme (gCM@MnAu) for enhanced cancer immunotherapy by inducing activating the stimulator interferon genes (STING) pathway. In tumor microenvironment (TME), gCM@MnAu initiates reaction generates abundant hydroxyl (•OH), resulting in improved chemodynamic therapy (CDT) boosted activation. addition, released Mn

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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Recent strategies for evoking immunogenic Pyroptosis in antitumor immunotherapy

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 366, P. 375 - 394

Published: Jan. 9, 2024

Pyroptosis is a specific type of programmed cell death (PCD) characterized by distinct morphological changes, including swelling, membrane blebbing, DNA fragmentation, and eventual lysis. closely associated with human-related diseases, such as inflammation malignancies. Since the initial observation pyroptosis in Shigella flexneri-infected macrophages more than 20 years ago, various pyroptosis-inducing agents, ions, small molecules, biological nanomaterials, have been developed for tumor treatment. Given that can activate body's robust immune response against promote formation long-term memory treatment, its status immunogenic self-evident. Therefore, should be used powerful anti-tumor strategy. However, there still lack comprehensive summary most recent advances pyroptosis-based cancer therapy. it vital to fill this gap inspire future drug design better induce cells undergo achieve advanced effects. In review, we summarize detail triggering adequate clearance based on treatment modalities, highlight material therapeutic advantages. Besides, also provide an outlook prospects emerging field next development.

Language: Английский

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High Immunogenic Cuproptosis Evoked by In Situ Sulfidation‐Activated Pyroptosis for Tumor‐Targeted Immunotherapy of Colorectal Cancer

Small Science, Journal Year: 2024, Volume and Issue: 4(3)

Published: Jan. 17, 2024

Despite the great potential of cuproptosis in tumor therapy, current cuproptosis‐based therapy still suffers from compromised efficiency immune activation. Pyroptosis, a proinflammatory cell death modality, provides good opportunity to induce immunogenic (ICD) and promote systemic response. However, synergistic pyroptosis has not been fully explored. Herein, it is discovered that Cu(II)‐based metal–organic framework (MOF) nanoparticles (NPs) can synergistically evoke ICD for high‐efficiency tumor‐targeted immunotherapy. Although MOF‐199 widely used immunogenicity unclear. Pluronic F127‐modified NPs ( F127 NPs) show dual‐responsiveness glutathione (GSH) hydrogen sulfide (H 2 S). Once entering cancer cells, dissociate GSH‐enriched microenvironment (TME) release copper ion copper‐overload‐mediated cuproptosis. Meanwhile, transform Cu 2− x S by situ sulfidation under H S‐enriched colorectal (CRC) TME. Under photothermal chemodynamic (PTT/CDT) NPs, caspase‐3 activated gasdermin E (GSDME)‐related triggered. The have proved superior antitumor immunity effect both vitro vivo experiments. This work new strategy achieve immunotherapy with high simple NPs.

Language: Английский

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Dual‐Pronged Attack: pH‐Driven Membrane‐Anchored NIR Dual‐Type Nano‐Photosensitizer Excites Immunogenic Pyroptosis and Sequester Immune Checkpoint for Enhanced Prostate Cancer Photo‐Immunotherapy

Advanced Science, Journal Year: 2023, Volume and Issue: 10(28)

Published: Aug. 6, 2023

Prostate cancer (PCa) is a frustrating immunogenic "cold" tumor and generally receives unsatisfied immunotherapy outcomes in the clinic. Pyroptosis an excellent cell death form that can effectively activate antitumor immune response, promote cytotoxic T-lymphocyte infiltration, convert tumors from to "hot." However, vivo application of pyroptosis drugs seriously limited, upregulation PD-L1 caused by photo-immunotherapy further promotes escape. Herein, new nano-photosensitizer (YBS-BMS NPs-RKC) with pH-response integrating induction checkpoint blockade developed. The pH-responsive polymer equipped membrane anchoring peptide RKC used as carrier encapsulated near-infrared-activated semiconductor photosensitizer YBS PD-1/PD-L1 complex small molecule inhibitor BMS-202. pH-driven membrane-anchoring activation YBS-BMS NPs-RKC clearly demonstrated. In vitro studies have shown this dual-pronged therapy stimulates powerful response suppress primary progression evokes long-term memory inhibit relapse metastasis. This work provides effective self-synergistic platform for PCa idea developing more biocompatible photo-controlled inducers.

Language: Английский

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Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 34(7)

Published: Nov. 5, 2023

Abstract Cancer immunotherapy has the potential to revolutionize treatment of malignant tumors, but its effectiveness is limited by low immune response rate and immune‐related adverse events. Pyroptosis, as an inflammatory programmed cell death type, triggers strong acute antitumor immunity, converting “cold” tumors “hot”. Particularly, biomaterials loading pyroptosis inducers targeting tumor microenvironment engineer pyroptosis, have achieved great progress in recent years. Herein, design strategy, mechanism pathway, role induce cancer are comprehensively reviewed. The present review focuses on application biomaterials‐induced immunotherapy, including nanogel, polymer prodrug, nanovesicle, mesoporous material. Additionally, synthesis a series stimuli‐responsive nanoplatforms, glutathione‐responsive, pH‐responsive, reactive oxygen species‐responsive, enzyme‐mimicking catalytic performance, described. Meanwhile, it augments multiple processes uptake, antigen presentation, T‐cell activation, expansion. Finally, perspectives pyroptosis‐mediated inflammation break through vascular basement membrane barrier achieving efficient volcanic penetration discussed. Artificial intelligence, multi‐omics analysis, anthropogenic animal models organoids presented, aiming provide guidance assistance for constructing effective controllable pyroptosis‐engineered improving immunotherapy.

Language: Английский

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Nanodrugs mediate TAMs-related arginine metabolism interference to boost photodynamic immunotherapy

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 367, P. 248 - 264

Published: Jan. 29, 2024

Language: Английский

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Recent advances in light-triggered cancer immunotherapy

Journal of Materials Chemistry B, Journal Year: 2024, Volume and Issue: 12(11), P. 2650 - 2669

Published: Jan. 1, 2024

Combining phototherapies, particularly PDT and PTT, with immunotherapy synergistically stimulates immune responses, offering promising strategies for effective cancer treatment prevention of recurrence.

Language: Английский

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Bioorthogonal/Ultrasound Activated Oncolytic Pyroptosis Amplifies In Situ Tumor Vaccination for Boosting Antitumor Immunity

ACS Nano, Journal Year: 2024, Volume and Issue: 18(13), P. 9413 - 9430

Published: March 24, 2024

Personalized in situ tumor vaccination is a promising immunotherapeutic modality. Currently, seeking immunogenic cell death (ICD) to generate vaccines still mired by insufficient immunogenicity and an entrenched immunosuppressive microenvironment (TME). Herein, series of tetrazine-functionalized ruthenium(II) sonosensitizers have been designed screened for establishing bioorthogonal-activated vaccine via oncolytic pyroptosis induction. Based on nanodelivery-augmented bioorthogonal metabolic glycoengineering, the original selectively remolded introduce artificial target bicycle [6.1.0] nonyne (BCN) into membrane. Through specific ligation with intratumoral BCN receptors, can realize precise membrane-anchoring synchronous click-activation desired sites. Upon ultrasound (US) irradiation, activated intensively disrupt membrane dual type I/II reactive oxygen species (ROS) generation high-efficiency sonodynamic therapy (SDT). More importantly, severe damage eminently evoke maximize reverse TME, ultimately eliciting powerful durable systemic antitumor immunity. The US-triggered certified effectively inhibit growths primary distant tumors, suppress metastasis recurrence "cold" models. This bioorthogonal-driven tumor-specific induction strategy has great potential development robust vaccines.

Language: Английский

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