Cuproptosis: Harnessing Transition Metal for Cancer Therapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(20), P. 19581 - 19599

Published: Oct. 11, 2023

Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act constituents of metalloenzymes involved cellular metabolism, function signaling molecules to regulate the proliferation metastasis tumors, are integral components metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate occurrence programmed cell death (PCD), known cuprotosis, cancer cells. This modulation occurs through disruption tumor metabolism induction proteotoxic stress. discovery uncovers a mode interaction between transition metals proteins, emphasizing intricate link homeostasis metabolism. Moreover, they provide innovative therapeutic strategies for precise diagnosis treatment malignant tumors. At crossroads chemistry oncology, we undertake comprehensive review elucidating molecular mechanisms underpinning cuproptosis. Additionally, summarize current nanotherapeutic approaches target cuproptosis an overview available laboratory clinical methods monitoring this process. In context emerging concepts, challenges, opportunities, emphasize significant potential nanotechnology advancement field.

Language: Английский

---

Engineered Bacteria Labeled with Iridium(III) Photosensitizers for Enhanced Photodynamic Immunotherapy of Solid Tumors

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(43)

Published: Sept. 5, 2023

Despite metal-based photosensitizers showing great potential in photodynamic therapy for tumor treatment, the application of is intrinsically limited by their poor cancer-targeting properties. Herein, we reported a photosensitizer-bacteria hybrid, Ir-HEcN, via covalent labeling an iridium(III) photosensitizer to surface genetically engineered bacteria. Due its intrinsic self-propelled motility and hypoxia tropism, Ir-HEcN selectively targets penetrates deeply into tissues. Importantly, capable inducing pyroptosis immunogenic cell death cells under irradiation, thereby remarkably evoking anti-tumor innate adaptive immune responses vivo leading regression solid tumors combinational immunotherapy. To best our knowledge, first metal complex decorated bacteria enhanced

Language: Английский

---

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 8991 - 9003

Published: March 21, 2024

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λem = 1105 nm), as first example Ru(II) supramolecular ICD inducer. synergistically potentiates immunomodulatory and reduces adverse through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting tumor cells, precision organelle localization, improved penetration/retention capabilities. Specifically, demonstrates excellent depth-activated ROS production (∼1 cm), resistance to diffusion, anti-ROS quenching. Moreover, exhibits promising results cellular uptake generation cancer cells multicellular spheroids. Importantly, induces more efficient an ultralow dose (10 μM) compared conventional agent, oxaliplatin (300 μM). In vivo experiments further confirm Ru1105's potency inducer, eliciting CD8+ T depleting Foxp3+ effects. Our research lays foundation for design secure exceptionally potent metal-based agents immunotherapy.

Language: Английский

---

Dendritic Nanomedicine with Boronate Bonds for Augmented Chemo‐Immunotherapy via Synergistic Modulation of Tumor Immune Microenvironment

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(2)

Published: Sept. 25, 2023

Unsatisfied tumor accumulation of chemotherapeutic drugs and a complicated immunosuppressive microenvironment diminish the immune response rate therapeutic effect. Surface modification these with target ligands can promote their cellular internalization, but modified may be subjected to unexpected recognition clearance. Herein, phenylboronic acid (PBA) group-shieldable dendritic nanomedicine that integrates an immunogenic cell death (ICD)-inducing agent (epirubicin, Epi) indoleamine 2,3-dioxgenase 1 (IDO1) inhibitor (NLG919) is reported for chemo-immunotherapy. This NLG919-loaded Epi-conjugated PEGylated dendrimers bridged boronate bonds (NLG919@Epi-DBP) maintains stable nanostructure during circulation. Under moderate acidic condition, PBA group exposes sialic residue on membrane enhance internalization penetration NLG919@Epi-DBP. At pH 5.0, NLG919@Epi-DBP rapidly disassembles release incorporated Epi NLG919. triggers robust ICD cells evokes strong response. In addition, inhibition IDO1 activity downregulates metabolism L-tryptophan kynurenine, leading reduction in recruitment modulation microenvironment. Collectively, this promising strategy has been demonstrated evoke as well remodel enhanced chemo-immunotherapeutic

Language: Английский

---

Reactive oxygen nanobiocatalysts: activity-mechanism disclosures, catalytic center evolutions, and changing states

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(19), P. 6838 - 6881

Published: Jan. 1, 2023

This review offers a comprehensive and timely summarization of the most recent breakthroughs future trends in creating reactive oxygen nanobiocatalysts, which guides their broad applications diverse biomedical biological fields.

Language: Английский

---

Activation of the cGAS-STING pathway by a mitochondrial DNA-targeted emissive rhodium(iii) metallointercalator

Chemical Science, Journal Year: 2023, Volume and Issue: 14(25), P. 6890 - 6903

Published: Jan. 1, 2023

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) pathway is a key mediator innate immunity involved in cancer development and treatment. roles mitochondrial DNA (mtDNA) immunotherapy have gradually emerged. Herein, we report highly emissive rhodium(iii) complex (Rh-Mito) as the mtDNA intercalator. Rh-Mito can specifically bind to cause cytoplasmic release fragments activate cGAS-STING pathway. Moreover, activates retrograde signaling by disturbing metabolites epigenetic modifications, which alters nuclear genome methylation landscape influence expression genes related immune pathways. Finally, demonstrate that ferritin-encapsulated elicits potent anticancer activities evokes intense responses vivo intravenous injection. Overall, for first time small molecules targeting pathway, gives insights into biomacromolecule-targeted immunotherapeutic agents.

Language: Английский

---

When near-infrared fluorescence meets supramolecular coordination complexes: Challenges and opportunities of metallacycles/metallacages in precision biomedicine

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 493, P. 215320 - 215320

Published: July 7, 2023

Language: Английский

---

Developing a Ruthenium(III) Complex to Trigger Gasdermin E-Mediated Pyroptosis and an Immune Response Based on Decitabine and Liposomes: Targeting Inhibition of Gastric Tumor Growth and Metastasis

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(18), P. 13072 - 13085

Published: Sept. 13, 2023

To develop next-generation metal drugs with high efficiency and low toxicity for targeting inhibition of gastric tumor growth metastasis, we not only optimized a series ruthenium (Ru, III) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes to obtain Ru(III) complex (4b) remarkable cytotoxicity in vitro but also constructed 4b-decitabine (DCT)/liposome (Lip) delivery system (4b-DCT-Lip). The vivo results showed that 4b-DCT-Lip had stronger capacity inhibit metastasis than 4b-DCT addressed the co-delivery problems improved their ability. Furthermore, confirmed mechanism 4b-DCT/4b-DCT-Lip inhibiting tumor. DCT-upregulated gasdermin E (GSDME) was cleaved by 4b-activated caspase-3 afford GSDME-N terminal then aggregated form nonselective pores on cell membrane tumor, thereby inducing pyroptosis pyroptosis-induced immune response.

Language: Английский

---

Evoking Ferroptosis by Synergistic Enhancement of a Cyclopentadienyl Iridium‐Betulin Immune Agonist

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(48)

Published: Oct. 13, 2023

Abstract Ferroptosis is a form of programmed cell death driven by iron‐dependent lipid peroxidation (LPO) with the potential for antitumor immunity activation. In this study, nonferrous cyclopentadienyl metal‐based ferroptosis inducer [Ir(Cp*)(Bet)Cl]Cl ( Ir‐Bet ) was developed metal‐ligand synergistic enhancement (MLSE) strategy involving reaction [Ir(Cp*)Cl] 2 Cl natural product Betulin. The fusion Betulin iridium (Ir‐Cp*) species as not only tremendously enhanced antiproliferative activity toward cancer cells, but also activated ferritinophagy iron homeostasis regulation PI3K/Akt/mTOR cascade inhibition lower dosage Betulin, and then evoked an immune response nuclear factor kappa‐B (NF‐κB) activation Ir‐Cp* species. Further immunogenic (ICD) occurred remarkable through glutathione (GSH) depletion, peroxidase 4 (GPX4) deactivation ferritinophagy. An in vivo vaccination experiment demonstrated desirable effects increasing ratio cytotoxic T cells (CTLs)/regulatory (Tregs).

Language: Английский

---

Metal N-heterocyclic carbene complexes as potential metallodrugs in antitumor therapy

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 514, P. 215941 - 215941

Published: May 18, 2024

Language: Английский

---