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

Novel 2-(5-Arylthiophen-2-yl)-benzoazole Cyclometalated Iridium(III) dppz Complexes Exhibit Selective Phototoxicity in Cancer Cells by Lysosomal Damage and Oncosis DOI Creative Commons
Jana Kašpárková, Alba Hernández-García, Hana Kostrhunová

и другие.

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 67(1), С. 691 - 708

Опубликована: Дек. 23, 2023

A second-generation series of biscyclometalated 2-(5-aryl-thienyl)-benzimidazole and -benzothiazole Ir(III) dppz complexes [Ir(C^N)2(dppz)]+, Ir1–Ir4, were rationally designed synthesized, where the aryl group attached to thienyl ring was p-CF3C6H4 or p-Me2NC6H4. These new assessed as photosensitizers explore structure–activity correlations for their potential use in biocompatible anticancer photodynamic therapy. When irradiated with blue light, exhibited high selective potency across several cancer cell lines predisposed therapy; benzothiazole derivatives (Ir1 Ir2) best performers, Ir2 being also activatable green red light. Notably, when irradiated, induced leakage lysosomal content into cytoplasm HeLa cells oncosis-like death. The capability Ir photoinduce death 3D spheroids has been demonstrated. investigated can catalytically photo-oxidate NADH photogenerate 1O2 and/or •OH cell-free media.

Язык: Английский

Процитировано

20
A ferroptosis-reinforced nanocatalyst enhances chemodynamic therapy through dual H2O2 production and oxidative stress amplification DOI
Xiaoyu Zhu, Tianyu Wang, Hao‐Ran Jia

и другие.

Journal of Controlled Release, Год журнала: 2024, Номер 367, С. 892 - 904

Опубликована: Фев. 24, 2024

Язык: Английский

Процитировано

8
Novel Re(I) Complexes as Potential Selective Theranostic Agents in Cancer Cells and In Vivo in Caenorhabditis elegans Tumoral Strains DOI Creative Commons
Alicia Marco, Pezhman Ashoo, Samanta Hernández‐García

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(10), С. 7891 - 7910

Опубликована: Март 7, 2024

A series of rhenium(I) complexes the type fac-[Re(CO)3(N^N)L]0/+, Re1–Re9, was synthesized, where N^N = benzimidazole-derived bidentate ligand with an ester functionality and L chloride or pyridine-type ligand. The new compounds demonstrated potent activity toward ovarian A2780 cancer cells. most active complexes, Re7–Re9, incorporating 4-NMe2py, exhibited remarkable in 3D HeLa spheroids. emission red region Re9, which contains electron-deficient benzothiazole moiety, allowed its operability as a bioimaging tool for vitro vivo visualization. Re9 effectivity tested two different C. elegans tumoral strains, JK1466 MT2124, to broaden oncogenic pathways studied. results showed that able reduce tumor growth both strains by increasing ROS production inside Moreover, selectivity compound cancerous cells it did not affect neither development nor progeny nematodes.

Язык: Английский

Процитировано

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

You‐Liang Zeng,

Liu‐Yi Liu,

Tianzhu Ma

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(49)

Опубликована: Авг. 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.

Язык: Английский

Процитировано

8
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

Процитировано

1