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

A NIR‐Light‐Activated and Lysosomal‐Targeted Pt(II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep‐Seated Tumors DOI

Chonglu Li,

Le Tu, Yuling Xu

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(37)

Опубликована: Май 22, 2024

Though platinum (Pt)-based complexes have been recently exploited as immunogenic cell death (ICD) inducers for activating immunotherapy, the effective activation of sufficient immune responses with minimal side effects in deep-seated tumors remains a formidable challenge. Herein, we propose first example near-infrared (NIR) light-activated and lysosomal targeted Pt(II) metallacycle (1) supramolecular ICD inducer. 1 synergistically potentiates immunomodulatory response via multiple-regulated approaches, involving NIR light excitation, boosted reactive oxygen species (ROS) generation, good selectivity between normal tumor cells, enhanced penetration/retention capabilities. Specifically, has excellent depth-activated ROS production (~7 mm), accompanied by strong anti-diffusion anti-ROS quenching ability. In vitro experiments demonstrate that exhibits significant cellular uptake generation cells well respective multicellular spheroids. Based on these advantages, induces more efficient an ultralow dose (i.e., 5 μM) compared clinical inducer-oxaliplatin (300 μM). vivo, vaccination further serves potent inducer through eliciting CD8

Язык: Английский

Процитировано

15
MOFs‐Based Magnetic Nanozyme to Boost Cascade ROS Accumulation for Augmented Tumor Ferroptosis DOI
Ying Yuan, Bo Chen,

Xingxing An

и другие.

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(20)

Опубликована: Март 26, 2024

The emerging cell death modality of ferroptosis has garnered increasing attention for antitumor treatment but still suffers from low therapeutic efficacy. A metal-organic frameworks (MOFs)-based magnetic nanozyme (PZFH) comprising porphyrin-based Zr-MOF (PCN) on zinc ferrite (ZF) nanoparticles modified with hyaluronic acid, delivering excellent magnetophotonic response efficient ferroptosis, is reported here. PZFH shows multienzyme-like cascade activity encompassing a photon-triggered oxidase-like catalysis to generate O

Язык: Английский

Процитировано

14
A Cyclometalated Ruthenium(II) Complex Induces Oncosis for Synergistic Activation of Innate and Adaptive Immunity DOI
Tao Feng, Zixin Tang, Jun Shu

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(31)

Опубликована: Май 21, 2024

Abstract An optimal cancer chemotherapy regimen should effectively address the drug resistance of tumors while eliciting antitumor‐immune responses. Research has shown that non‐apoptotic cell death, such as pyroptosis and ferroptosis, can enhance immune response. Despite this, there been limited investigation reporting on mechanisms oncosis its correlation with Herein, we designed synthesized a Ru(II) complex targeted nucleus mitochondria to induce oncosis. Briefly, disrupts DNA, which active polyADP‐ribose polymerase 1, accompanied by ATP consumption porimin activation. Concurrently, mitochondrial damage endoplasmic reticulum stress result in release Ca 2+ ions increased expression Calpain 1. Subsequently, specific pore proteins 1 promote cristae destruction or vacuolation, ultimately leading membrane rupture. The analysis RNA sequencing demonstrates initiate oncosis‐associated pathway activate both innate adaptive immunity. In vivo experiments have confirmed promotes dendritic maturation awakens cytotoxic T lymphocytes but also activates inducing polarization macrophages towards an M1 phenotype.

Язык: Английский

Процитировано

14
Rhenium(I) coordinated carbon nitride as type II immunogenic cell death inducers for enhancing photoimmunotherapy against triple-negative breast cancer DOI

Fangmian Wei,

Jinzhe Liang,

Zhushuang Tan

и другие.

Chemical Engineering Journal, Год журнала: 2024, Номер 485, С. 150154 - 150154

Опубликована: Март 2, 2024

Язык: Английский

Процитировано

13
Disrupting Intracellular Homeostasis by Copper‐Based Nanoinducer with Multiple Enzyme‐Mimicking Activities to Induce Disulfidptosis‐Enhanced Pyroptosis for Tumor Immunotherapy DOI
Xiao‐Kang Jin,

S Y Zhang,

Shi‐Man Zhang

и другие.

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Окт. 29, 2024

Given the crucial role of abnormal homeostasis in tumor cells for maintaining their growth, it may be more efficient with less effort to develop anti-tumor strategies that target multiple combined mechanisms by disrupting intracellular homeostasis. Here, a copper-based nanoinducer (CGBH NNs) enzyme-like activities is designed and constructed induce disulfidptosis-enhanced pyroptosis through effective immunotherapy. Within microenvironment (TME), CGBH NNs can disrupt glucose inhibit NADPH production, leading accumulation cystine, which further blocked substrate key enzyme synthesizing glutathione. Subsequently, cascade catalytic reactions involving (glutathione peroxidase-like, oxidase peroxidase-like activities), produce massive reactive oxygen species (ROS) redox homeostasis, resulting pyroptosis. The undergoing immunogenic release various cytosolic contents inflammatory factors, eliciting robust immune responses facilitating cell infiltration, reprogramming immunosuppressive TME. After combination checkpoint blockade therapy, effectively suppress growth prolong survival time tumor-bearing mice. This work presents novel paradigm trigger destroying

Язык: Английский

Процитировано

11
Hollow Calcium/Copper Bimetallic Amplifier for Cuproptosis/Paraptosis/Apoptosis Cancer Therapy via Cascade Reinforcement of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction DOI
Weijun Xu,

Aili Suo,

Abdalrheem Jarelnaby Musa Aldai

и другие.

ACS Nano, Год журнала: 2024, Номер 18(43), С. 30053 - 30068

Опубликована: Окт. 16, 2024

The endoplasmic reticulum (ER) and mitochondria are essential organelles that play crucial roles in maintaining cellular homeostasis. simultaneous induction of ER stress mitochondrial dysfunction represents a promising yet challenging strategy for cancer treatment. Herein, hollow calcium–copper bimetallic nanoplatform is developed as cascade amplifier to reinforce breast For this purpose, we report facile method preparing CaCO3 (HCC) nanoparticles by regulating the dissolution–recrystallization process amorphous CaCO3, D@HCC-CuTH meticulously fabricated sequentially coating disulfiram-loaded HCC with copper coordination polymer hyaluronan. In tumor cells, dithiocarbamate–copper complex generated situ liberated disulfiram Cu2+ inhibits ubiquitin–proteasome system, causing irreversible intracellular Ca2+ redistribution. Meanwhile, induces via triggering self-amplifying loop burst, reactive oxygen species augment. Additionally, dihydrolipoamide S-acetyltransferase oligomerization mitochondria, further exacerbating damage cuproptosis. Collectively, amplification synergistically induce cuproptosis–paraptosis–apoptosis trimodal cell death pathway, which demonstrates significant efficacy suppressing growth. This study presents paradigm synchronously inducing subcellular organelle disorders boost multimodal therapy.

Язык: Английский

Процитировано

10
Chemiluminescent transition metal complexes: Mechanisms and applications DOI
Jinghui Zhu,

Mingrui Gu,

Yahui Chen

и другие.

Coordination Chemistry Reviews, Год журнала: 2025, Номер 530, С. 216495 - 216495

Опубликована: Фев. 5, 2025

Язык: Английский

Процитировано

2
Bi-anthracene based ruthenium and iridium metalla-rectangles: Coordination driven self-assembly and anti-cancer activities DOI
Gajendra Gupta, Paritosh Patel, Junseong Lee

и другие.

Inorganic Chemistry Communications, Год журнала: 2025, Номер unknown, С. 113916 - 113916

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Synergistic Enhancement of Ferroptosis via Mitochondrial Accumulation and Photodynamic-Controlled Release of an Organogold(I) Cluster Prodrug DOI

Kunran Xiao,

Da‐Yong Hou,

Ni‐Yuan Zhang

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Effective delivery and controlled release of metallo-prodrugs with sustained activation rapid response feed the needs precise medicine in metal chemotherapeutics. However, gold-based anticancer drugs often suffer from detoxification binding extracellular transfer by sulfur-containing peptides. To address this challenge, we integrate a thiol-activated prodrug strategy newly prepared hypercoordinated carbon-centered gold(I) clusters (HCGCs) their photosensitization character to augment mitochondrial Au(I) tumors. In contrast distorted [CAu4] kernel pentanuclear HCGC compound [A5], its dimeric congener [A9] exhibits symmetrical [{CAu4}-Au-{CAu4}] structure remarkable hypercarbon-to-Au4 electron donation. This unique arrangement results microsecond long metal-metal-to-ligand charge excited state relative nanosecond intraligand [A5]. Upon light irradiation at 560 nm, generates active 1O2 oxidize glutathione (GSH) into poorly coordinating GSSG cytoplasm finally promotes subcellular HCGCs mitochondria. Moreover, GSH further triggers consecutive [AuPPh3]+ ions inhibit cytoplasmic peroxidase GPX4 thioredoxin reductase TrxR2, which collectively result accelerated ferroptosis human bladder cancer EJ cells show excellent antitumor performance mouse tumor models.

Язык: Английский

Процитировано

1
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 DOI
Wenjuan Li, Shanhe Li, Gang Xu

и другие.

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(18), С. 13072 - 13085

Опубликована: Сен. 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.

Язык: Английский

Процитировано

23