Activating the cGAS-STING Pathway by Manganese-Based Nanoparticles Combined with Platinum-Based Nanoparticles for Enhanced Ovarian Cancer Immunotherapy DOI

Xiangling Zhang,

Dongsheng Tang, Haihua Xiao

и другие.

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Recent research has demonstrated that activating the cGAS-STING pathway can enhance interferon production and activation of T cells. A manganese complex, called TPA-Mn, was developed in this context. The reactive oxygen species (ROS)-sensitive nanoparticles (NPMn) loaded with TPA-Mn are developed. NPMn activates via cGAS (i.e., 1.6-fold enhancement P-STING), which turn increases secretion pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-2). This promotes dendritic cell maturation, enhances infiltration cytotoxic lymphocytes, reduces percentage immunosuppressive regulatory In addition, it is crucial to emphasize cisplatin-induced DNA damage potentially trigger pathway. NPMn, combination low-dose NPPt, a carrier Cis(IV) prodrug capable causing damage, augments significantly tumor immune microenvironment (TIME). Furthermore, combined anti-PD-1 antibody, NPPt+NPMn shows synergistic efficacy both ovarian cancer peritoneal metastases recurrence models. It not only effectively eliminates tumors but also induces strong memory response, providing promising strategy for clinical management cancer. work offers design manganese-based immunotherapy.

Язык: Английский

Cuproptosis: Harnessing Transition Metal for Cancer Therapy DOI
Wuyin Wang, Wentao Mo, Zishan Hang

и другие.

ACS Nano, Год журнала: 2023, Номер 17(20), С. 19581 - 19599

Опубликована: Окт. 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.

Язык: Английский

Процитировано

87
Engineered Bacteria Labeled with Iridium(III) Photosensitizers for Enhanced Photodynamic Immunotherapy of Solid Tumors DOI

Wenkai Lin,

Yu Liu, Jinhui Wang

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(43)

Опубликована: Сен. 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

Язык: Английский

Процитировано

52
Dendritic Nanomedicine with Boronate Bonds for Augmented Chemo‐Immunotherapy via Synergistic Modulation of Tumor Immune Microenvironment DOI Open Access
Yunkun Li, Yahui Wu,

Zaixiang Fang

и другие.

Advanced Materials, Год журнала: 2023, Номер 36(2)

Опубликована: Сен. 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

Язык: Английский

Процитировано

49
Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle DOI
Le Tu,

Chonglu Li,

Qihang Ding

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(13), С. 8991 - 9003

Опубликована: Март 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.

Язык: Английский

Процитировано

47
Metal N-heterocyclic carbene complexes as potential metallodrugs in antitumor therapy DOI
Yifan Zhang,

Yi-Kui Yin,

Heng Zhang

и другие.

Coordination Chemistry Reviews, Год журнала: 2024, Номер 514, С. 215941 - 215941

Опубликована: Май 18, 2024

Язык: Английский

Процитировано

18
Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics DOI Creative Commons
Huayun Shi, Rafael C. Marchi, Peter J. Sadler

и другие.

Angewandte Chemie International Edition, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Photoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms action to combat resistance current therapy. We highlight recent progress in design platinum, ruthenium, iridium, gold other transition complexes, especially for applications as anticancer anti‐infective agents. In particular, understanding excited state chemistry related identification bioactive species (excited metallomics/pharmacophores) is important. metallodrugs are classified here photocatalysts, photorelease agents ligand‐activated Their activation wavelengths, cellular action, experimental theoretical metallomics states photoproducts discussed explore strategies investigation photoactivatable metallodrugs. These have potential clinical Photodynamic Therapy (PDT), Photoactivated Chemotherapy (PACT) Photothermal (PTT).

Язык: Английский

Процитировано

4
Reactive oxygen nanobiocatalysts: activity-mechanism disclosures, catalytic center evolutions, and changing states DOI
Sujiao Cao, Yanping Long, Sutong Xiao

и другие.

Chemical Society Reviews, Год журнала: 2023, Номер 52(19), С. 6838 - 6881

Опубликована: Янв. 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.

Язык: Английский

Процитировано

35
Activation of the cGAS-STING pathway by a mitochondrial DNA-targeted emissive rhodium(iii) metallointercalator DOI Creative Commons
Yue Zheng, Xiaoxiao Chen, Dongyang Zhang

и другие.

Chemical Science, Год журнала: 2023, Номер 14(25), С. 6890 - 6903

Опубликована: Янв. 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.

Язык: Английский

Процитировано

24
When near-infrared fluorescence meets supramolecular coordination complexes: Challenges and opportunities of metallacycles/metallacages in precision biomedicine DOI
Yuling Xu,

You Dou,

Qian Li

и другие.

Coordination Chemistry Reviews, Год журнала: 2023, Номер 493, С. 215320 - 215320

Опубликована: Июль 7, 2023

Язык: Английский

Процитировано

24
Evoking Ferroptosis by Synergistic Enhancement of a Cyclopentadienyl Iridium‐Betulin Immune Agonist DOI Open Access

Mengdi Lv,

Yue Zheng,

Jian Wu

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(48)

Опубликована: Окт. 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).

Язык: Английский

Процитировано

24