At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment DOI Creative Commons
Tatyana V. Korneenko, Nikolay B. Pestov, Ivan Nevzorov

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(12), P. 1675 - 1675

Published: Dec. 1, 2023

The evolutionary conserved DNA-sensing cGAS-STING innate immunity pathway represents one of the most important cytosolic systems that is activated in response to viral invasion and/or damage integrity nuclear envelope. key outcome this production interferon, which subsequently stimulates transcription hundreds genes. In oncology, situation complex because may serve either anti- or pro-oncogenic roles, depending on context. prevailing understanding when immune by sensing DNA, such as DNA released from ruptured micronuclei, it results attracts cytotoxic cells destroy tumors. However, tumor have adjusted significant chromosomal instability, particularly relapsed, treatment-resistant cancers, often supports cancer progression, fostering epithelial-to-mesenchymal transition (EMT). Here, we review intricate terms its association with giving special attention pancreatic ductal adenocarcinoma and gliomas. As development new cGAS-STING-modulating small molecules immunotherapies oncolytic viruses involves serious challenges, highlight several recent fundamental discoveries, proton-channeling function STING. These discoveries guiding lights for potential pharmacological advancements.

Language: Английский

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

40
cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation DOI Creative Commons
Jingwen Liu, Jing Zhou,

Yuling Luan

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 9, 2024

Abstract Background Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression organ degeneration, but the mechanism regulation of crosstalk network remain unclear. Main body abstract Cellular stress disrupts mitochondrial homeostasis, facilitates opening permeability transition pore leakage DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, subsequently induces activation onset pyroptosis. Meanwhile, inflammasome-associated protein caspase-1, Gasdermin D, CARD domain ASC potassium channel are involved in regulating pathway. Importantly, this has a cascade amplification effect that exacerbates immuno-inflammatory response, worsening pathological process autoimmune diseases. Given importance innate immunity, it is emerging new avenue explore mechanisms multiple disease pathogenesis. Therefore, efforts define strategies selectively modulate different settings have been or ongoing. In review, we will describe how mechanistic understanding driving possible therapeutics targeting network, focusing on interacting regulatory proteins, pathways, hub between inflammasomes, Short conclusion This review aims provide insight into roles pyroptosis, highlight some promising directions future research intervention.

Language: Английский

Citations

30
Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity DOI Creative Commons
Yanlin Zhu, Xinxin Wang, Lili Feng

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 8, 2024

Pyroptosis, an immunogenic programmed cell death, could efficiently activate tumor immunogenicity and reprogram immunosuppressive microenvironment for boosting cancer immunotherapy. However, the overexpression of SLC7A11 promotes glutathione biosynthesis maintaining redox balance countering pyroptosis. Herein, we develop intermetallics modified with glucose oxidase (GOx) soybean phospholipid (SP) as pyroptosis promoters (Pd

Language: Английский

Citations

27
Tunable Ion-Release Biodegradable Nanoparticles Enhanced Pyroptosis for Tumor Immunotherapy DOI
Lin Liu, Kaiyan Huang, Xia Sun

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 317, P. 123111 - 123111

Published: Jan. 15, 2025

Language: Английский

Citations

2
Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy DOI

Meng‐Jie Zhang,

Yuanyuan Wang,

Lin‐Lin Han

et al.

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

Citations

26
Biodegradable pyroptosis inducer with multienzyme-mimic activity kicks up reactive oxygen species storm for sensitizing immunotherapy DOI
Junrong Wang,

Luying Qiao,

Guo‐Qing Zhu

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 370, P. 438 - 452

Published: May 6, 2024

Language: Английский

Citations

11
Post-translational modifications as a key mechanism for herpes simplex virus type I evasion of host innate immunity DOI Creative Commons
Yongxing Zhang, Jingying Xie, Ying Feng

et al.

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 11, 2025

Herpes simplex virus type 1 (HSV-1) is a DNA that infects humans and establishes long-term latency within the host. Throughout its prolonged interaction with host, HSV-1 evades innate immune system by encoding own proteins. Post-translational modifications (PTMs) of these proteins play crucial roles in their function, activity, interactions other factors modifying specific amino acids, thereby enabling diverse range protein functions. This review explores mechanisms PTMs HSV-1-encoded proteins, such as phosphorylation, ubiquitination, deamidation, SUMOylation, during infection latency. These are essential for suppressing host immunity, facilitating viral replication, elucidating crosstalk among various post-translational modifications.

Language: Английский

Citations

1
Assembly of Glycopeptides in Living Cells Resembling Viral Infection for Cargo Delivery DOI
Feng Tian, Ruochen Guo,

Chunxia Wu

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(28)

Published: April 24, 2024

Abstract Self‐assembly in living cells represents one versatile strategy for drug delivery; however, it suffers from the limited precision and efficiency. Inspired by viral traits, we here report a cascade targeting‐hydrolysis‐transformation (THT) assembly of glycosylated peptides holistically resembling infection efficient cargo delivery combined tumor therapy. We design peptide via incorporating β‐galactose‐serine residue into bola‐amphiphilic sequences. Co‐assembling with two counterparts containing irinotecan (IRI) or ligand TSFAEYWNLLSP (PMI) results formation co‐assemblies SgVEIP , which target cancer β‐galactose‐galectin‐1 association undergo galactosidase‐induced morphological transformation. While GSH‐reduction causes release IRI co‐assemblies, PMI moieties p53 facilitate cell death binding protein MDM2. Cellular experiments show membrane targeting, endo‐/lysosome‐mediated internalization situ nanofibers cytoplasm . This THT process enables secreting Gal‐1 overexpressing β‐galactosidase. In vivo studies illustrate enhanced accumulation retention thereby suppressing growth. Our findings demonstrate an mimicking infection, thus providing new route therapy future.

Language: Английский

Citations

8
Artificial Bacteriophages for Treating Oral Infectious Disease via Localized Bacterial Capture and Enhanced Catalytic Sterilization DOI Creative Commons
Xiaocan Liu,

Danfeng Luo,

Shuang Dai

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(41)

Published: Aug. 19, 2024

Abstract With the rapid emergence of antibiotic‐resistant pathogens, nanomaterial‐assisted catalytic sterilization has been well developed to combat pathogenic bacteria by elevating level reactive oxygen species including hydroxyl radical (·OH). Although promising, ultra‐short lifetime and limited diffusion distance ·OH severely limit their practical antibacterial usage. Herein, rational design preparation novel virus‐like copper silicate hollow spheres (CSHSs) are reported, as applications robust artificial bacteriophages for localized bacterial capture enhanced in treatment oral infectious diseases. During whole process killing, CSHSs can efficiently via shortening between CSHSs, produce massive around bacteria, further iinducing admirable effect inhibition. By using mucosal infection periodontitis typical diseases, it is easily found that populations lesions animals after fall sharply, well‐developed nanosystem decrease inflammatory reaction promote hard or soft tissue repair. Together, high Fenton‐like activity, strong affinity, excellent overall safety nanoplatform promise its great therapeutic potential disinfection.

Language: Английский

Citations

8
Iridium(III) Photosensitizers Induce Simultaneous Pyroptosis and Ferroptosis for Multi‐Network Synergistic Tumor Immunotherapy DOI

You‐Liang Zeng,

Liu‐Yi Liu,

Tianzhu Ma

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(49)

Published: Aug. 24, 2024

Abstract The integration of pyroptosis and ferroptosis hybrid cell death induction to augment immune activation represents a promising avenue for anti‐tumor treatment, but there is lack research. Herein, we developed two iridium (III)‐triphenylamine photosensitizers, IrC IrF , with the capacity disrupt redox balance induce photo‐driven cascade damage DNA Kelch‐like ECH‐associated protein 1 (KEAP1). absent in melanoma 2 (AIM2)‐related cytoplasmic nucleic acid‐sensing pathway, triggered by damaged DNA, leads gasdermin D (GSDMD)‐mediated pyroptosis. Simultaneously, iron homeostasis, regulated KEAP1/nuclear factor erythroid 2‐related (NRF2)/heme oxygenase (HO‐1) serves as pivotal bridge, facilitating not only E (GSDME)‐mediated non‐canonical pyroptosis, also synergy glutathione peroxidase 4 (GPX4) depletion. collaborative action generates synergistic effect that elicits immunogenic death, stimulates robust response effectively inhibits tumor growth vivo. Our work introduces first metal‐based small molecule dual‐inducers potent cancer immunotherapy, highlights significance homeostasis vital hub connecting effects ferroptosis.

Language: Английский

Citations

8