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

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy DOI Creative Commons
Qiang Lü,

Dongquan Kou,

Shenghan Lou

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 2, 2024

Abstract Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, immune cells, plays a crucial role response modulation. Nanoparticles, engineered to reshape TME, shown promising results enhancing by facilitating targeted These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, encourage T infiltration. Biomimetic further enhance increasing internalization agents cells such as cells. Moreover, exosomes, whether naturally secreted body or bioengineered, been explored regulate TME immune-related affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated pH, redox, light conditions, exhibit potential accelerate co-application with checkpoint inhibitors is an emerging strategy boost anti-tumor immunity. With their ability induce long-term immunity, nanoarchitectures are structures development. This review underscores critical overcoming current driving advancement modification.

Language: Английский

Citations

144
Ultrathin Clay Nanoparticles‐Mediated Mutual Reinforcement of Ferroptosis and Cancer Immunotherapy DOI Open Access
Jianping Liu,

Jiezhao Zhan,

Ye Zhang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(9)

Published: Nov. 8, 2023

Ferroptosis-triggered immunogenic cell death (ICD) is widely adopted to potentiate the body's antitumor immunity by catalyzing production of toxic reactive oxygen species (ROS). However, efficacy ferroptosis and immunotherapy greatly restricted intracellular abundant glutathione (GSH) immunosuppressive tumor microenvironment (TME). Herein, a facile bottom-up method for solvent-free synthesis ultrathin manganese (Mn)-based layered double hydroxide nanosheets with high loading efficiency pro-inflammatory cytokine interferon (IFNγ) (IFNγ/uMn-LDHs) proposed mutually reinforce systemic immunity. The introduction ions significantly contributes GSH depletion hydroxyl radical generation, which can be further enhanced IFNγ delivery-induced SLC7A11 downregulation. ICD effect after cooperates intrinsic immunomodulatory property IFNγ/uMn-LDHs facilitate maturation dendritic cells (DCs) priming T cells. secretion from activated CD8

Language: Английский

Citations

66
“Multi‐in‐One” Yolk‐Shell Structured Nanoplatform Inducing Pyroptosis and Antitumor Immune Response Through Cascade Reactions DOI
Yuying Wang, Shulan Li,

Xiao‐Yang Zhang

et al.

Small, Journal Year: 2024, Volume and Issue: 20(30)

Published: Feb. 25, 2024

Abstract Pyroptosis, a new mode of regulatory cell death, holds promising prospect in tumor therapy. The occurrence pyroptosis can trigger the release damage‐associated molecular patterns (DAMPs) and activate antitumor immune response. Moreover, enhancing intracellular reactive oxygen species (ROS) generation effectively induce pyroptosis. Herein, an integrated nanoplatform (hCZAG) based on zeolitic imidazolate framework‐8 (ZIF‐8) with Cu 2+ Zn as active nodes glucose oxidase (GOx) loading is constructed to evoke GOx elevate hydrogen peroxide (H 2 O ) levels regulate unfavorable microenvironment (TME). be reduced + by endogenous overexpressed GSH both exert Fenton‐like activity promote ROS amplify oxidative stress. In addition, accumulation leads aggregation lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), thus resulting cuproptosis. Notably, outburst induced hCZAG activates Caspase‐1 proteins, cleavage gasdermin D (GSDMD), induces Pyroptosis further elicits adaptive response, leading immunogenic death (ICD). This study provides effective strategies for triggering pyroptosis‐mediated immunotherapy achieving improved therapeutic effects.

Language: Английский

Citations

13
Zinc Coordination Lipid Nanoparticles Co‐Delivering Calcium Peroxide and Chelating STING agonist for Enhanced Cancer Metalloimmunotherapy DOI
Qian Qiu, Jiexin Li, Ren He

et al.

Small, Journal Year: 2024, Volume and Issue: 20(46)

Published: Aug. 8, 2024

Abstract Metalloimmunotherapy has achieved great preclinical success against malignant tumors. Nonetheless, the limited immune cell infiltration and impaired immunogenicity within tumor microenvironment (TME) significantly hinder its translation to clinical applications. In this study, a zinc coordination lipid nanoparticle is developed loaded with calcium peroxide hydrate (CaO 2 ) nanoparticles STING agonist diABZI‐2, which termed A‐CaO ‐Zn‐LNP. The release of Zn 2+ from ‐Zn‐LNP overload synergistically induced immunogenic death (ICD). addition, CaO can consume H + oxygen (O under acidic conditions. This treatment increased pH alleviated hypoxia TME. Along cGAS‐STING activation by ultimately results in enhanced anti‐tumor systemic immunity long‐term memory via alleviating immunosuppressive microenvironment. Taken together, offers new nanoplatform that expands application for cancer metalloimmunotheray.

Language: Английский

Citations

12
Harnessing phytochemicals: innovative strategies to enhance cancer immunotherapy DOI Creative Commons
Qianru Zhu, Ruonan Zhang, Min Jin Ha

et al.

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: 79, P. 101206 - 101206

Published: Feb. 1, 2025

Cancer immunotherapy has revolutionized cancer treatment, but therapeutic ineffectiveness-driven by the tumor microenvironment and immune evasion mechanisms-continues to limit its clinical efficacy. This challenge underscores need explore innovative approaches, such as multimodal immunotherapy. Phytochemicals, bioactive compounds derived from plants, have emerged promising candidates for overcoming these barriers due their immunomodulatory antitumor properties. review explores synergistic potential of phytochemicals in enhancing modulating responses, reprogramming microenvironment, reducing immunosuppressive factors. Integrating with conventional strategies represents a novel approach mitigating resistance outcomes. For instance, nab-paclitaxel shown checkpoint inhibitors, while QS-21 synergistically enhances efficacy vaccines. Furthermore, we highlight recent advancements leveraging nanotechnology engineer improved bioavailability targeted delivery. These innovations hold great promise optimizing application phytochemicals. However, further large-scale studies are crucial fully integrate into immunotherapeutic regimens effectively.

Language: Английский

Citations

1
Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 Modulator DOI Creative Commons

Fei Xia,

Yuqian Lu, Zipeng Gong

et al.

Exploration, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

ABSTRACT The insufficient infiltration and functional inhibition of CD8 + T cells due to tumor microenvironment (TME) are considered enormous obstacles anti‐tumor immunotherapy. Herein, a pH‐responsive core‐shell manganese phosphate nanomodulator co‐loading siPD‐L1 Mn 2+ into nanoparticles coated with hyaluronic acid was prepared, which aimed at the bidirectional reprogramming microenvironment: (1) “Brakes off,” restoring function by knockdowning PD‐L1 expression cells; (2) “Step on accelerator,” promoting in tumors tissue based multidimensional immune effects (immunogenic cell death induced enhancing cGAS‐STING pathway, proliferation maturation relative cells). Additionally, this strategy could induce macrophage polarization inhibit regulatory site. This work provided reprogram TME for an enhanced comprehensive effect triple negative breast cancer, offers robust method immunotherapy future clinical applications.

Language: Английский

Citations

1
Advances in Nanoplatform-based Multimodal Combination Therapy Activating STING Pathway for Enhanced Anti-tumor Immunotherapy DOI
Huizhong Zhang, Xiaohan Xu,

Shiman Li

et al.

Colloids and Surfaces B Biointerfaces, Journal Year: 2025, Volume and Issue: 250, P. 114573 - 114573

Published: Feb. 18, 2025

Language: Английский

Citations

1
In situ forming AIEgen-alginate hydrogel for remodeling tumor microenvironment to boost FLASH immunoradiotherapy DOI
Meng Lyu, Tianfu Zhang, Zhirong Bao

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 320, P. 123281 - 123281

Published: March 20, 2025

Language: Английский

Citations

1
Water‐Dispersible MXene Governs Glycolysis for Cancer Synergistic Therapy DOI
Jinfeng Liu,

Yuwen Gong,

Dandan Wang

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Abstract Targeted delivery of glucose oxidase (GOx) using MXene remains a great challenge due to its poor dispersion and susceptibility oxidation, the hypoxia high glutathione (GSH) contents make situation even more worrying. Herein, bovine serum albumin‐mediated non‐chemical modification strategy is developed, endowing titanium carbide with long‐time water‐dispersion further integrating it as glycolysis‐controllable therapy system without any chemotherapeutic agents. The also constructs an effective O 2 cycling GSH degradation pathway, which fundamentally adjusts tumor microenvironment greatly elevates both in vivo vitro effects. Reactive oxygen species are generated disrupt balance oxidative stress. Moreover, reduced efficiency mitochondrial energy production significantly inhibits level glycolysis hinders supply. study presents cancer treatment combining starvation/photothermal therapy, has superior anti‐cancer effects dual reducing levels diminishing cellular capacity.

Language: Английский

Citations

1
Biomimetic MOF‐Based Nano‐Immunoactivator via Disruption of Ion Homeostasis for Strengthened Tumor Microwave‐Immunotherapy DOI

Zengzhen Chen,

Wenna Guo,

Longfei Tan

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(36)

Published: March 4, 2024

Abstract Immunogenic cell death (ICD) is a promising strategy for anticancer immunity by inducing antigen‐presenting maturation. However, the traditional ICD inducers, such as chemotherapeutic agents, have largely hampered their application severe side effects and low tumor selectivity. The changes intra/extracellular ion concentrations affect growth metastasis of cells. Interference with homeostasis can induce elicit immune responses. Here, biomimetic Ga‐based metal–organic framework (MOF) coated red blood cell–platelet fusion membrane (RPM), that is, 5‐fluorouracil@GaMOF@RPM (5‐FUGR) nano‐immunoactivator, reported highly efficient inducer enhanced microwave (MW)‐immunotherapy. Following intravenous administration, 5‐FUGR accumulates to site via RPM modification‐mediated long circulation active targeting. structure undergoes degradation releases Ga 3+ . MW combined high disrupts intracellular homeostasis, which leads oxidative stress Ca 2+ retention promote apoptosis More importantly, not only completely eradicates 4T1 primary tumors, but also induces ICD, initiation, memory inhibit metastatic recurrence tumor. Thus, 5‐FUGR, strong inducer, provides new insights into achieving in combination other therapies.

Language: Английский

Citations

8