GSH-responsive and Mitochondria-targeting Multifunctional Nanoplatform for MR imaging-guided enhanced chemotherapy of Glioma by Reshaping the Tumor Immune Microenvironment DOI Creative Commons
Guangrong Zheng, Tengfei Ke, Wen Zhao

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Abstract Despite considerable progress in glioma research, present therapeutic approaches continue to be insufficiently efficacious, predominantly owing challenging hindrances conveying chemotherapy drugs across the blood-brain barrier (BBB) and reshaping immunosuppressive tumor microenvironment (TME). In this study, a multifunctional nanoplatform was developed comprising poly-lactide-co-glycolide (PLGA) encapsulated with MnO2 nanoparticles, triphenylphosphonium (TPP) conjugated doxorubicin (DOX), Angiopep-2 (Ang) for magnetic resonance imaging-guided enhanced of glioma. The role Ang promotes BBB penetration cell targeting, while TPP allows an increased concentration Ang-PMT NPs mitochondria. Upon exposure high glutathione (GSH) within TME, disintegrate rapidly, resulting production Mn2+ subsequent release DOX. released DOX directly eradicates cells catalyzes mitochondrial DNA release, leading immunogenic death (ICD) activation cGAS-STING pathway. Furthermore, produced also activates pathway, thereby TME enhancing demonstrated notable inhibition growth comparison control groups. It is anticipated that innovative approach may offer promising prospects management malignant clinical management.

Language: Английский

cGAS/STING signaling pathway in gynecological malignancies: From molecular mechanisms to therapeutic values DOI Creative Commons
Danyang Zhang, Bingxue Zhang

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 30, 2025

Gynecological cancers, including cervical, ovarian, and endometrial malignancies, remain a significant global health burden, exacerbated by disparities in access to preventive measures such as HPV vaccination routine screening. The cGAS/STING signaling pathway, pivotal mechanism innate immunity, detects cytosolic DNA from pathogens or cellular damage, triggering immune responses via type I interferons inflammatory cytokines. This pathway’s dual role gynecological either promoting antitumor immunity facilitating tumor evasion, makes it compelling target for innovative therapies. article outlines cGAS/STING’s influence on microenvironments, surveillance, inflammation, with emphasis molecular mechanisms driving cancer progression. It explores interactions between damage response pathways modulation, highlighting the impact of activation suppression cancers. therapeutic potential STING agonists, PARP inhibitors, targeted immunotherapies is reviewed, demonstrating how these approaches can boost responses, counteract chemotherapy resistance, improve patient outcomes. study also discusses strategies leveraging enhance efficacy address tumor-mediated suppression, providing insights into future directions personalized treatments.

Language: Английский

Citations

1
Mitochondrial DNA-activated cGAS-STING pathway in cancer: Mechanisms and therapeutic implications DOI

Lintao Xia,

Xiuli Yan, Hui Zhang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1880(1), P. 189249 - 189249

Published: Dec. 17, 2024

Language: Английский

Citations

5
A metal anion strategy to induce pyroptosis combined with STING activation to synergistically amplify anti-tumor immunity DOI
Zifan Pei, Nan Jiang, Fei Gong

et al.

Materials Today, Journal Year: 2024, Volume and Issue: 80, P. 23 - 39

Published: Aug. 16, 2024

Language: Английский

Citations

4
Orchestrated Copper-Loaded Nanoreactor for Simultaneous Induction of Cuproptosis and Immunotherapeutic Intervention in Colorectal Cancer DOI Creative Commons
Jiasheng Li, Shanshan Ma,

Lin Qiu-hua

et al.

Materials Today Bio, Journal Year: 2024, Volume and Issue: 29, P. 101326 - 101326

Published: Nov. 9, 2024

Ion interference, including intracellular copper (Cu) overload, disrupts cellular homeostasis, triggers mitochondrial dysfunction, and activates cell-specific death channels, highlighting its significant potential in cancer therapy. Nevertheless, the insufficient Cu ions transported by existing ionophores, which are small molecules with short blood half-lives, inevitably hamper effectiveness of cuproptosis. Herein, ESCu@HM nanoreactor, self-assembled from integration H-MnO

Language: Английский

Citations

4
Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors DOI Creative Commons

Xiaohong Ying,

Qiaohui Chen, Yongqi Yang

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Dec. 23, 2024

Language: Английский

Citations

4
USP34 regulates PIN1-cGAS-STING axis-dependent ferroptosis in cervical cancer via SUMOylation DOI
Dan Liao, Yumeng Cui,

Lijuan Shi

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 113968 - 113968

Published: Jan. 5, 2025

Language: Английский

Citations

0
A novel small molecule NJH-13 induces pyroptosis via the Ca2+ driven AKT-FOXO1-GSDME signaling pathway in NSCLC by targeting TRPV5 DOI Creative Commons

Xianxiang Dong,

Jiahui Nie,

Aijun Huang

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Pyroptosis represents a mode of programmed necrotic cell death (PCD), mediated by members gasdermin family (GSDMs), such as GSDME. It is emerging promising approach for combating cancer. Notably, GSDME the key modulator switch between apoptosis and pyroptosis in cells. However, often downregulated many malignancies, including lung adenocarcinoma. To identify novel inducers non-small cancer (NSCLC) dissect underlying mechanism. was examined live imaging, PI/Hoechst/Annexin V staining, LDH release assay, ELISA, western blot assays. DARTS, CETSA, molecular docking used to target NJH-13. RNA-seq, qPCR, chromatin immunoprecipitation (ChIP), dual luciferase assays were elucidate In this study, NJH-13, an N-containing heterocycle, screened out identified possess ability activate GSDME, consequently triggering NSCLC By using DARTS strategy, transient receptor potential cation channel subfamily member 5 (TRPV5) NJH-13 increased intracellular calcium level triggered oxidative stress, both which are critical events leading Mechanistically, enhanced transcription via protein kinase B (AKT)/forkhead box factor O1 (FOXO1) signaling pathway. ChIP revealed that FOXO1 bound directly promoter region thus GSDME-mediated pyroptosis. Pharmacological genetic activation AKT or inhibition partially rescued NJH-13-induced pyroptotic death. Moreover, treatment suppressed tumor growth vivo. Taken together, our results TRPV5 distinctive manipulating provided evidence functions anti-cancer agent capable

Language: Английский

Citations

0
Hyaluronic acid-mediated targeted nano-modulators for activation of pyroptosis for cancer therapy through multichannel regulation of Ca2+ overload DOI
Linwei Li,

Zihan Xing,

Jinyu Wang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 299, P. 140116 - 140116

Published: Jan. 20, 2025

Language: Английский

Citations

0
Tumor-targeted near-infrared/ultraviolet-triggered photothermal/gas therapy nanoplatform for effective cancer synergistic therapy DOI
Xiaomei Wu,

Zhongyin Chen,

Jinyu Wang

et al.

Colloids and Surfaces B Biointerfaces, Journal Year: 2025, Volume and Issue: 249, P. 114530 - 114530

Published: Jan. 20, 2025

Language: Английский

Citations

0
Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer Therapy DOI Creative Commons
Linhong Zhong, Xun Guo, Liming Deng

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Piezocatalyst-enabled sonopiezoelectric therapy offers noninvasive treatment with high spatiotemporal selectivity, yet existing piezocatalysts are limited by suboptimal efficacy, cancer cell resistance to oxidative stress, and biosafety concerns. Here, hafnia (HfO2), one of the only few FDA-approved inorganic nanomaterials for clinical trials, is identified as a promising piezocatalyst translational potential enzymatic PANoptosis-boosted nanocatalytic therapy. Specifically, engineered transition metal-substituted HfO2 nanocatalysts synthesized optimize piezoelectric enzyme-mimicking activities. Among these, Mn-substituted 20% Mn ratio (HMO) demonstrates superior performance in sono-triggered reactive oxygen species generation, attributed its reduced bandgap increased vacancies. HMO also exhibits multiple activities, including peroxidase (POD), catalase (CAT), glutathione (GPx), amplifying stress through tumor-specific catalytic reactions. These dual effects enable activation PANoptosis elicit robust antitumor immune response. Biological evaluations show significant tumor suppression responses HMO-mediated Unlike utilizing radiosensitization ability clinic, this work unveils distinctive effect multienzymatic activities HfO2-based biomedical applications, holding overcome challenges radiation damage associated radiotherapy.

Language: Английский

Citations

0