METTL3 inhibition-activated cGAS/STING axis enhances immunotherapy and PARP inhibitor sensitivity of lung carcinoma DOI
Jiawang Zhou,

Jiaxin He,

Yunqing Lu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Abstract The cGAS/STING-mediated type I interferon response can augment antitumor activity, while the regulatory factors within this innate immune remain elusive. Herein we found that RNA m 6 A methyltransferase METTL3 was upregulated in lung carcinoma tissues. Elevated level correlated with diminished CD8 + T cell infiltration and cancer progression patients. deficiency exacerbated nuclear DNA leakage into cytoplasm, activating cGAS pathway thereby enhancing anti-tumor immunity. Mechanistically, reduced homologous recombination repair efficacy via downregulation of MSH5, a mutS family protein involved mismatch repair, leading to increased cytosolic levels. methylation A2521 MSH5 stabilized its mRNA binding IGF2BP2. On other hand, A1545 at CDS decreased stability regulates expression. Functionally, knockdown sensitized cells PARP inhibitors. In vivo clinical data confirmed positive roles inhibition-activated cGAS/STING axis tumor growth adenocarcinoma progression. Collectively, inhibition activates immunity induction expression, which turn regulate inhibitor carcinoma.

Language: Английский

Biometallic ions and derivatives: a new direction for cancer immunotherapy DOI Creative Commons
Lin Zhao,

Yajun Gui,

Jing Cai

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 15, 2025

Biometallic ions play a crucial role in regulating the immune system. In recent years, cancer immunotherapy has become breakthrough treatment, achieving good efficacy wide range of cancers with its specificity and durability advantages. However, existing therapies still face challenges, such as tolerance escape. (e.g. zinc, copper, magnesium, manganese, etc.) can assist enhancing through activation cells, enhancement tumor antigen presentation, improvement microenvironment. addition, biometallic derivatives directly inhibit cell progression offer possibility effectively overcoming limitations current by promoting responses reducing immunosuppressive signals. This review explores potential application prospects immunotherapy, providing new ideas for future clinical metal part helping to guide development more effective safe therapeutic regimens.

Language: Английский

Citations

2
A pH-Responsive and Guanidinium-Rich Nanoadjuvant Efficiently Delivers STING Agonist for Cancer Immunotherapy DOI

Xiao Juan Lu,

Heming Xia, Wei Gao

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

As natural agonists of the stimulator interferon genes (STING), cyclic dinucleotides (CDNs) have been identified as promising immunotherapies that trigger a potent immune response against tumors. However, low stability, rapid clearance, inadequate cellular uptake, and inefficient cytosol localization heavily hinder therapeutic efficacy hydrophilic negatively charged 2′, 3′-cyclic-GMP-AMP (cGAMP). How to efficiently deliver cGAMP into endoplasmic reticulum (ER) activate STING for priming remains challenging. Here, we report pH-responsive guanidinium-rich nanoagonist (nPGSA) delivery cGAMP. Compared with free cGAMP, nPGSA achieves up 37.4-fold enhancement internalization. The pH-sensitive guanidinium-functional design facilitates quick release endosome escape, thus enabling precise ER targeting 33.9-fold amplification sensibilization. Furthermore, through modulation tumor-associated macrophage (TAM) polarization, elicits antigen-specific sustained tumor regression in melanoma- neuroblastoma-bearing mice. Our study provides strategy it offers insights function modulating microenvironment cancer immunotherapy.

Language: Английский

Citations

2
Multi‐Metallic Nanosheets Reshaping Immunosuppressive Tumor Microenvironment through Augmenting cGAS‐STING Innate Activation and Adaptive Immune Responses for Cancer Immunotherapy DOI Creative Commons
Yuxuan Peng,

Shuang Liang,

Dan Liu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(38)

Published: Aug. 9, 2024

The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore surveillance system for robust activation, vast efforts are devoted to normalizing TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed potent anti-tumor immunity by reversing Mn-LDH synthesized via one-step hydrothermal method. In addition inherent proton neutralization capacity LDH, introduction manganese oxide endows LDH with an additional ability produce oxygen. effectively releases Mn

Language: Английский

Citations

10
Photochemical bomb: Precision nuclear targeting to activate cGAS-STING pathway for enhanced bladder cancer immunotherapy DOI
Dexiang Feng,

Xiaoying Kang,

He Wang

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: unknown, P. 123126 - 123126

Published: Jan. 1, 2025

Language: Английский

Citations

0
Mitoxantrone‐Encapsulated ZIF‐8 Enhances Chemo‐Immunotherapy via Amplified Immunogenic Cell Death DOI Creative Commons
Junhong Li,

Wenxing Lv,

Ziwei Han

et al.

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

Published: Feb. 14, 2025

Abstract Chemo‐immunotherapy, combining systemic chemotherapeutic drugs and immune checkpoint blockers, is a promising paradigm in cancer treatment. However, challenges such as limited induction of responses toxicity have hindered its clinical applications. Here, zeolite imidazolate framework‐8 (ZIF‐8) that encapsulates mitoxantrone (MIT), an cell death (ICD)‐inducing agent (MIT@ZIF‐8), synthesized using one‐pot aqueous‐phase process. ZIF‐8 serves dual‐functional nanomaterial for chemo‐immunotherapy: carrier to enhance tumor uptake MIT improved chemotherapy efficacy, pyroptosis inducer amplify MIT‐induced ICD augmented anti‐tumor responses. As result, vivo administration MIT@ZIF‐8 markedly inhibits growth both immunologically “hot” colon “cold” prostate cancer. Moreover, treatment increases the abundance cytotoxic CD8 + T cells reduces amount immunosuppressive regulatory tumors, thereby enhancing immunity sensitizing anti‐CTLA‐4 immunotherapy. In summary, offers highly translational approach chemo‐immunotherapy.

Language: Английский

Citations

0
Piezo‐STING Agonists Enhance Tumor Penetration and Catalytic‐immunotherapy DOI Open Access
Zhuo Li, Yuan Meng,

H. F. Liu

et al.

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 16, 2025

Abstract The cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)‐stimulator of interferon genes (STING) signaling pathway is an important innate immune that has shown remarkable potential in cancer immunotherapy. However, the clinical therapeutic efficacy limited due to insufficient penetration STING agonists into tumors. In this study, a special piezo‐STING agonist (ZnS‐Cur@CM, Z/C@M) composed zinc sulfide nanosheets, curcumin, and tumor cell membranes based on principle piezocatalytic for water splitting generate gas designed, which effectively reduces intratumoral delivery resistance, markedly enhancing depth drug Under ultrasound, Z/C@M rapidly decomposes interstitial fluid produce hydrogen, leading decreased pressure increased accumulation within tumor. Additionally, reactive oxygen species generated by piezocatalysis damage mitochondria cells, resulting release mitochondrial DNA activation cGAS‐STING pathway. Moreover, released Zn 2+ acidic microenvironment further enhances signal transduction. reduce through improve tumors, also activates treatment. This study provides novel perspective

Language: Английский

Citations

0
Unleashing the Potential of Metal Ions in cGAS-STING Activation: Advancing Nanomaterial-Based Tumor Immunotherapy DOI Creative Commons

Xingyin Li,

Shaojie Xu,

Ziliang Su

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Immunotherapy is a critical modality in cancer treatment with diverse activation pathways. In recent years, the stimulator of interferon genes (STING) signaling pathway has exhibited significant potential tumor immunotherapy. This exerts notable antitumor effects by activating innate and adaptive immunity regulating immune microenvironment. Various metal ions have been identified as effective activators STING and, through design synthesis nanodelivery platforms, applied immunotherapy well combination therapies, such chemotherapy, chemodynamic therapy, photodynamic vaccines. Metal nanomaterials showcase unique advantages immunotherapy; however, there are still aspects that require optimization. review systematically examines existing metal-based nanomaterials, elaborates on mechanisms which different activate pathway, discusses their application models therapies. We also provide comparative analysis over other methods. Our exploration highlights broad prospects treatment, offering new insights directions for advancement

Language: Английский

Citations

0
PD-1-engineered manganese-based nanoplatform loaded with CXCL9 induces ICD and intensifies T-cell infiltration for melanoma treatment DOI Creative Commons
Pei Ma,

Jueshuo Guo,

Peng Li

et al.

Advanced Composites and Hybrid Materials, Journal Year: 2025, Volume and Issue: 8(3)

Published: May 9, 2025

Language: Английский

Citations

0
Nano-immunomodulator amplifies STING activation in tumor-associated macrophages for cancer immunotherapy DOI

Shuang Liang,

Haiyan Ma, Yue Liu

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113846 - 113846

Published: May 1, 2025

Language: Английский

Citations

0
Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy DOI Creative Commons
Yanan Ren, Fei Wu,

Linlin Huo

et al.

Materials Today Bio, Journal Year: 2024, Volume and Issue: 29, P. 101328 - 101328

Published: Nov. 6, 2024

Acute kidney injury (AKI) induced by cisplatin (DDP), which is accompanied with the generation of reactive oxygen species (ROS), a severe side effect during treatment and restricts application DDP. In this study, we develop ultrasmall Mn

Language: Английский

Citations

1