Construction of Active Sites‐Accessible Au8 Clusters for Intensive Tumor Pyroptosis DOI Creative Commons

Qiu‐Xu Zang,

Wei Tong Chen, Wenjing Zhang

et al.

Aggregate, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

ABSTRACT Atomically precise gold nanoclusters (NCs), possessing characteristics of molecules and nanoparticles, offer a promising solution to the challenges faced by existing pyroptosis inducers. Their abilities catalyze generation reactive oxygen species enhance radiosensitization position them as effective agents for activating pyroptosis. However, their catalytic efficiency is often compromised limited geometrically accessible spaces around active sites lack suitable ligands. Leveraging exposed metal centers in mononuclear organometallic catalysts tunable ligand NCs, herein, ethynylferrocene (EFc) was utilized amplify peroxidase (POD)‐like activity NCs establishing unshielded center electron donor‐acceptor interaction between EFc Au core. The resulting 8 Fe 2 with excellent POD‐mimicking could efficiently trigger inducing intracellular oxidative stress. Moreover, potential deplete glutathione enable magnetic resonance imaging, also induce ferroptosis serve diagnostic tool tumors. All these processes can be further potentiated X‐ray radiation, taking advantage high atomic number gold. This work opens new avenues engineering properties broadens applications biomedicine.

Language: Английский

Engineered platelets as targeted protein degraders and application to breast cancer models DOI
Yu Chen,

Samira Pal,

Wen Li

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Language: Английский

Citations

7
Integrating Proteolysis‐Targeting Chimeras (PROTACs) with Delivery Systems for More Efficient and Precise Targeted Protein Degradation DOI

Jiachan Lin,

Zirui Chen, Dan Zhang

et al.

Macromolecular Rapid Communications, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Targeted protein degradation (TPD) using the proteolysis-targeting chimeras (PROTACs) is emerging as a revolutionary technology, offering potential strategy for cancer treatment by inducing of overexpressed oncogenic proteins in tumors. PROTACs function recruiting E3 ligases and utilizing ubiquitin-proteasome pathway (UPS) to catalyze target proteins. Compared traditional small molecules inhibitors, exhibit enhanced selectivity, ability overcome drug resistance, traditionally deemed "undruggable". However, poor water solubility low cellular permeability significantly limit their pharmacokinetic properties, while systemic toxicity may hinder clinical application. To address these limitations, strategies that integrate with delivery systems are gaining attention. This review summarizes latest advancements various enhance vivo efficacy reduce off-target effects PROTACs, including prototype nanoparticles, covalent modification-based prodrug strategies, innovative multi-headed designs, microneedle systems, discussing design principles associated challenges. The combination potent multifunctional holds promise accelerating translation improving therapeutic treatment.

Language: Английский

Citations

1
Engineering materials for pyroptosis induction in cancer treatment DOI Creative Commons
Jiayi Liu,

Taili Chen,

XianLing Liu

et al.

Bioactive Materials, Journal Year: 2023, Volume and Issue: 33, P. 30 - 45

Published: Nov. 7, 2023

Cancer remains a significant global health concern, necessitating the development of innovative therapeutic strategies. This research paper aims to investigate role pyroptosis induction in cancer treatment. Pyroptosis, form programmed cell death characterized by release pro-inflammatory cytokines and formation plasma membrane pores, has gained attention as potential target for therapy. The objective this study is provide comprehensive overview current understanding its discusses concept relationship with other forms death, such apoptosis necroptosis. It explores immune activation combination also reviews use natural, biological, chemical, multifunctional composite materials cells. molecular mechanisms underlying these are discussed, along their advantages challenges findings highlight novel strategy treatment insights into different involved induction.

Language: Английский

Citations

13
Inhalable iron redox cycling powered nanoreactor for amplified ferroptosis-apoptosis synergetic therapy of lung cancer DOI

Linjing Wu,

Wenhao Wang,

Mengqin Guo

et al.

Nano Research, Journal Year: 2024, Volume and Issue: 17(6), P. 5435 - 5451

Published: Feb. 1, 2024

Language: Английский

Citations

5
Modulation of Metal Homeostasis for Cancer Therapy DOI

Ying Yang,

Huanhuan Fan, Zijian Guo

et al.

ChemPlusChem, Journal Year: 2024, Volume and Issue: 89(6)

Published: Feb. 7, 2024

Metal ions such as iron, zinc, copper, manganese, and calcium are essential for normal cellular processes, including DNA synthesis, enzyme activity, signaling, oxidative stress regulation. When the balance of metal homeostasis is disrupted, it can lead to various pathological conditions, cancer. Thus, understanding role in cancer has led development anti-tumor strategies that specifically target imbalance. Up now, diverse small molecule-based chelators, ionophores, complexes, metal-based nanomaterials have been developed restore metals or exploit dysregulation therapeutic purposes. They hold great promise inhibiting tumor growth, preventing metastasis, enhancing effectiveness existing therapies. In this review, we aim provide a comprehensive summary employed modulate therapy. Their modulation mechanisms succinctly described, their recent applications field therapy discussed. At end, limitations these approaches addressed, potential avenues future developments explored.

Language: Английский

Citations

5
A dynamic cascade DNA nanocomplex to synergistically disrupt the pyroptosis checkpoint and relieve tumor hypoxia for efficient pyroptosis cancer therapy DOI Creative Commons
Xiaoni Wang,

Xiyang Ge,

Min Zhang

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(19), P. 7079 - 7091

Published: Jan. 1, 2024

Pyroptosis has attracted widespread concerns in cancer therapy, while the therapeutic efficiency could be significantly restricted by using crucial pyroptosis checkpoint of autophagy and tumor hypoxia. Herein, a DNA nanocomplex (DNFs@ZnMn), containing cascade DNAzymes, promoter-like ZnO2-Mn nanozymes photosensitizers, was constructed one pot through rolling circle amplification reactions to induce disrupting autophagy. After targeting cells with high expression H+ glutathione, DNFs@ZnMn decomposed expose DNAzymes nanozymes. Then, sufficient metal ions O2 were released promote DNA/RNA cleavage relieving The DNAzyme-1 self-cleaved long strands Zn2+ as cofactor simultaneously exposed DNAzyme-2 cleave ATG-5 mRNA (with Mn2+ cofactor). This DNAzyme-mediated gene regulation process induced downregulation proteins disrupt Simultaneously, ZnO2 donated H2O2 generate adequate relieve hypoxia, obtaining highly cytotoxic 1O2 trigger pyroptosis. By dynamic silencing synergistic this weakened cellular resistance achieve efficient therapy both vitro vivo.

Language: Английский

Citations

5
Boarding pyroptosis onto nanotechnology for cancer therapy DOI

Weiyue Ban,

Zhichao Chen,

Tao Zhang

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 370, P. 653 - 676

Published: May 15, 2024

Language: Английский

Citations

5
Pyroptosis: Induction and inhibition strategies for immunotherapy of diseases DOI Creative Commons
Junjun Wu, Hong Wang, Pu Gao

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(10), P. 4195 - 4227

Published: June 28, 2024

Cell death is a central process for organismal health. Pyroptosis, namely pyroptotic cell death, recognized as critical type that disrupts membrane and triggers pro-inflammatory cytokine secretion

Language: Английский

Citations

3
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, Journal Year: 2024, Volume and Issue: 136(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

3
Intracellular metal ion-based chemistry for programmed cell death DOI
Y You, Zhongying Guo, Tyler Wolter

et al.

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Intracellular metal ions play essential roles in multiple physiological processes, including catalytic action, diverse cellular intracellular signaling, and electron transfer. It is crucial to maintain ion homeostasis which achieved by the subtle balance of storage release intracellularly along with influx efflux at interface cell membrane. Dysregulation has been identified as a key mechanism triggering programmed death (PCD). Despite importance initiating PCD, molecular mechanisms within these processes are infrequently discussed. An in-depth understanding review role PCD may better uncover novel tools for cancer diagnosis therapy. Specifically, calcium (Ca

Language: Английский

Citations

0