A Self‐Adaptive Pyroptosis Inducer: Optimizing the Catalytic Microenvironment of Nanozymes by Membrane‐Adhered Microbe Enables Potent Cancer Immunotherapy DOI
Wenjie Wang, Lu Zhang, Yanjie Zhang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(14)

Published: Dec. 28, 2023

Pyroptosis has garnered increasing attention in cancer immunotherapy. Moreover, plasma membrane damage by reactive oxygen species (ROS) is considered an effective strategy for promoting pyroptosis. However, the current tactics enhancing rupture pyroptosis are limited inherent drawbacks of ROS and immunosuppressive tumor microenvironment. Herein, a self-adaptive inducer (LPZ) designed integrating Lactobacillus rhamnosus GG (LGG) enzyme-like metal-organic framework to achieve potent LPZ can adhere cell membranes through interaction between pili LGG mucin cells. In particular, adaptive formula gradually enhance ability nanozymes produce creating acidic microenvironment anaerobic respiration. These results verify that could generate high levels both on within cells, leading pyroptotic death strong antitumor immunity. Meanwhile, eventually killed this process halt their respiration prevent potential biosafety concerns. Overall, work provides new inspiration design nanocatalytic drugs

Language: Английский

Bioactive inorganic nanomaterials for cancer theranostics DOI
Zifan Pei,

Huali Lei,

Liang Cheng

et al.

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(6), P. 2031 - 2081

Published: Jan. 1, 2023

Bioactive materials are a special class of biomaterials that can react in vivo to induce biological response or regulate functions, thus achieving better curative effect than traditional inert biomaterials. For cancer theranostics, compared with organic polymer nanomaterials, inorganic nanomaterials possess unique physical and chemical properties, have stronger mechanical stability on the basis maintaining certain bioactivity, easy be compounded various carriers (polymer carriers, etc.), so as achieve specific antitumor efficacy. After entering nanoscale, due nano-size effect, high surface area nanostructures, exhibit effects, which significantly influence interaction organisms. Therefore, research applications bioactive theranostics attracted wide attention. In this review, we mainly summarize recent progress also introduce definition, synthesis modification strategies nanomaterials. Thereafter, tumor imaging therapy, including microenvironment (TME) regulation, catalytic gas regulatory cell death immunotherapy, discussed. Finally, biosafety challenges mentioned, their future development opportunities prospected. This review highlights bioapplication

Language: Английский

Citations

125
Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy DOI Creative Commons
Liang Zhang, An Song,

Qi‐Chao Yang

et al.

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

Citations

95
Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors DOI Open Access

Luying Qiao,

Guo‐Qing Zhu, Tengfei Jiang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Oct. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Language: Английский

Citations

83
Activation of Pyroptosis Using AIEgen-Based sp2 Carbon-Linked Covalent Organic Frameworks DOI
Liang Zhang, Shu‐Cheng Wan, Jianyu Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(32), P. 17689 - 17699

Published: Aug. 8, 2023

Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect apoptosis resistance often limit therapeutic efficacy. Herein, we demonstrated first time that linking luminogens with aggregation-induced emission (AIEgens) into COF networks via vinyl linkages was an effective strategy construct nonmetallic pyroptosis inducers boosting antitumor immunity. Mechanistic investigations revealed formation linkage in AIE endowed it not only high brightness but also strong absorption ability, long lifetime, quantum yield favor generation reactive oxygen species eliciting pyroptosis. In addition, synergized system αPD-1 effectively eradicated primary distant tumors inhibited tumor recurrence metastasis bilateral 4T1 model.

Language: Английский

Citations

56
Sodium Bicarbonate Nanoparticles for Amplified Cancer Immunotherapy by Inducing Pyroptosis and Regulating Lactic Acid Metabolism DOI
Binbin Ding, Pan Zheng, Jia Tan

et al.

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

Citations

56
Pore Space Partition Approach of ZIF-8 for pH Responsive Codelivery of Ursolic Acid and 5-Fluorouracil DOI
Ziqi Zhou,

Qiaomei Ke,

Manni Wu

et al.

ACS Materials Letters, Journal Year: 2023, Volume and Issue: 5(2), P. 466 - 472

Published: Jan. 13, 2023

Metal–organic frameworks are smart carriers for controlled drug delivery due to large surface area and adjustable pore size. Current approaches can hardly utilize the space of MOFs thoroughly, greatly causing waste space. Here, Pore Space Partition (PSP) approach was employed achieve effective encapsulation pH-controlled codelivery two guest molecules. The ZIF-8 partitioned by molecule ursolic acid (UA), remaining filled with small 5-fluorouracil (5-FU), obtaining 5-FU&UA@ZIF-8 high loading capacity UA (12.80 wt %) 5-FU (11.20 %). Accompanied collapse in acidic surroundings, exhibited delivery. To our surprise, also showed pH responsive delivery, which did not exist before partition UA. Codelivery enable have good anticancer performance against 4T1 cells.

Language: Английский

Citations

49
Simultaneous Activation of Pyroptosis and cGAS‐STING Pathway with Epigenetic/ Photodynamic Nanotheranostic for Enhanced Tumor Photoimmunotherapy DOI Open Access

Feixiang Ding,

Junyan Liu, Kelong Ai

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(7)

Published: Oct. 5, 2023

Promoting innate immunity through pyroptosis induction or the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway activation has emerged as a potent approach to counteract immunosuppressive tumor microenvironment and elicit systemic antitumor immunity. However, current inducers STING agonists often suffer from limitations including instability, unpredictable side effects, inadequate intracellular expression gasdermin STING. Here, tumor-specific nanotheranostic platform that combines photodynamic therapy (PDT) with epigenetic simultaneously activate cGAS-STING in light-controlled manner is constructed. This involves development oxidation-sensitive nanoparticles (NP1) loaded photosensitizer TBE, along decitabine nanomicelles (NP2). NP2 enables restoration E (GSDME) expression, while NP1-mediated PDT facilitates release DNA fragments damaged mitochondria potentiate pathway, promotes caspase-3 cleave upregulated GSDME into pore-forming GSDME-N terminal. Subsequently, released inflammatory cytokines facilitate maturation antigen-presentation cells, triggering T cell-mediated Overall, this study presents an elaborate strategy for simultaneous photoactivation enabling targeted photoimmunotherapy immunotolerant tumors. innovative holds significant promise overcoming associated existing therapeutic modalities represents valuable avenue future clinical applications.

Language: Английский

Citations

48
Pyroptosis in health and disease: mechanisms, regulation and clinical perspective DOI Creative Commons
Yifan Liu,

Renjie Pan,

Yuzhen Ouyang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

Citations

37
Strategies for the development of metalloimmunotherapies DOI
Xiaoqi Sun, Xingwu Zhou, Xiaoyue Shi

et al.

Nature Biomedical Engineering, Journal Year: 2024, Volume and Issue: 8(9), P. 1073 - 1091

Published: June 24, 2024

Language: Английский

Citations

34
Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment DOI
Lin Liu,

Huali Lei,

Guanghui Hou

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(20), P. 12830 - 12844

Published: May 6, 2024

The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectively enhance antitumor immune response through gas-amplified metalloimmunotherapy with dual activation pyroptosis and STING pathway. bioactive MCSP exhibited ability rapidly release Ca2+, Mn2+, H2S in tumor microenvironment. disrupted buffer system cells by interfering oxidative phosphorylation pathway, leading overload-triggered pyroptosis. On other hand, H2S-mediated mitochondrial dysfunction further promoted DNA (mtDNA), enhancing effect Mn2+ on cGAS-STING signaling axis thereby activating immunosuppressed dendritic cells. released acted as an important synergist between Ca2+ modulating mechanisms bridge innate adaptive responses. combination NPs PD-1 immunotherapy achieved synergistic effects inhibited growth. This study reveals potential collaboration gas therapy provides idea for design nanoimmunomodulators rational regulation

Language: Английский

Citations

27