Advances of MnO2 nanomaterials as novel agonists for the development of cGAS-STING-mediated therapeutics DOI Creative Commons

Tangxin Zhang,

Chunmiao Hu,

Wenting Zhang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 19, 2023

As an essential micronutrient, manganese plays important role in the physiological process and immune process. In recent decades, cGAS-STING pathway, which can congenitally recognize exogenous endogenous DNA for activation, has been widely reported to play critical roles innate immunity against some diseases, such as infections tumor. Manganese ion (Mn2+) recently proved specifically bind with cGAS activate pathway a potential agonist, however, is significantly restricted by low stability of Mn2+ further medical application. one most stable forms manganese, dioxide (MnO2) nanomaterials have show multiple promising functions, drug delivery, anti-tumor anti-infection activities. More importantly, MnO2 are also found be candidate agonist transforming into Mn2+, indicates their regulations different diseased conditions. this review, we introduced methods preparation well biological Moreover, emphatically discussed detailed mechanisms activation converting Mn2+. And application disease treatment regulating might benefit future development novel targeted treatments based on nanoplatforms.

Language: Английский

Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation DOI Creative Commons
Kaiyuan Wang, Yang Li, Xia Wang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 23, 2023

The immunologically "cold" microenvironment of triple negative breast cancer results in resistance to current immunotherapy. Here, we reveal the immunoadjuvant property gas therapy with cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway activation augment aggregation-induced emission (AIE)-active luminogen (AIEgen)-based photoimmunotherapy. A virus-mimicking hollow mesoporous tetrasulfide-doped organosilica is developed for co-encapsulation AIEgen and manganese carbonyl fabricate nanoadjuvant. As tetra-sulfide bonds are responsive intratumoral glutathione, nanoadjuvant achieves tumor-specific drug release, promotes photodynamic therapy, produces hydrogen sulfide (H2S). Upon near-infrared laser irradiation, AIEgen-mediated phototherapy triggers burst carbon monoxide (CO)/Mn2+. Both H2S CO can destroy mitochondrial integrity induce leakage DNA into cytoplasm, serving as immunoadjuvants activate cGAS-STING pathway. Meanwhile, Mn2+ sensitize cGAS STING-mediated type I production. Consequently, potentiates photoimmunotherapy poorly immunogenic tumors female mice.

Language: Английский

Citations

145
MnOOH-Catalyzed Autoxidation of Glutathione for Reactive Oxygen Species Production and Nanocatalytic Tumor Innate Immunotherapy DOI

Piao Zhu,

Yinying Pu,

Min Wang

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(10), P. 5803 - 5815

Published: Feb. 27, 2023

The antioxidant system, signed with reduced glutathione (GSH) overexpression, is the key weapon for tumor to resist attack by reactive oxygen species (ROS). Counteracting ROS depletion GSH an effective strategy guarantee antitumor efficacy of nanocatalytic therapy. However, simply reducing concentration does not sufficiently improve response therapy intervention. Herein, a well-dispersed MnOOH nanocatalyst developed catalyze autoxidation and peroxidase-like reaction concurrently respectively promote H2O2 decomposition produce abundant such as hydroxyl radical (·OH), thereby generating highly superadditive catalytic therapeutic efficacy. Such that transforms endogenous "antioxidant" into "oxidant" may open new avenue development medicine. Moreover, released Mn2+ can activate sensitize cGAS-STING pathway damaged intratumoral DNA double-strands induced produced further macrophage maturation M1-polarization, which will boost innate immunotherapeutic Resultantly, simple medicine capable simultaneously catalyzing generation, mediating immune activation, holds great potential in treatment malignant tumors.

Language: Английский

Citations

86
Recent advances in Zn-MOFs and their derivatives for cancer therapeutic applications DOI Creative Commons
Minmin Li, Zhixin Zhang, Yamei Yu

et al.

Materials Advances, Journal Year: 2023, Volume and Issue: 4(21), P. 5050 - 5093

Published: Jan. 1, 2023

The use of zinc-based MOFs in a variety cancer treatments was comprehensively reviewed. advantages and disadvantages, as well the application prospects future, are also discussed.

Language: Английский

Citations

75
Simultaneous Activation of Pyroptosis and cGAS‐STING Pathway with Epigenetic/ Photodynamic Nanotheranostic for Enhanced Tumor Photoimmunotherapy DOI Open Access

Feixiang Ding,

Junyan Liu, Kelong Ai

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(7)

Published: Oct. 5, 2023

Promoting innate immunity through pyroptosis induction or the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway activation has emerged as a potent approach to counteract immunosuppressive tumor microenvironment and elicit systemic antitumor immunity. However, current inducers STING agonists often suffer from limitations including instability, unpredictable side effects, inadequate intracellular expression gasdermin STING. Here, tumor-specific nanotheranostic platform that combines photodynamic therapy (PDT) with epigenetic simultaneously activate cGAS-STING in light-controlled manner is constructed. This involves development oxidation-sensitive nanoparticles (NP1) loaded photosensitizer TBE, along decitabine nanomicelles (NP2). NP2 enables restoration E (GSDME) expression, while NP1-mediated PDT facilitates release DNA fragments damaged mitochondria potentiate pathway, promotes caspase-3 cleave upregulated GSDME into pore-forming GSDME-N terminal. Subsequently, released inflammatory cytokines facilitate maturation antigen-presentation cells, triggering T cell-mediated Overall, this study presents an elaborate strategy for simultaneous photoactivation enabling targeted photoimmunotherapy immunotolerant tumors. innovative holds significant promise overcoming associated existing therapeutic modalities represents valuable avenue future clinical applications.

Language: Английский

Citations

49
Biomimetic Nano-Drug Delivery System: An Emerging Platform for Promoting Tumor Treatment DOI Creative Commons
Xiujuan Han, Chunai Gong,

Qingru Yang

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 571 - 608

Published: Jan. 1, 2024

Abstract: With the development of nanotechnology, nanoparticles (NPs) have shown broad prospects as drug delivery vehicles. However, they exhibit certain limitations, including low biocompatibility, poor physiological stability, rapid clearance from body, and nonspecific targeting, which hampered their clinical application. Therefore, novel systems with improved biocompatibility high target specificity remains a major challenge. In recent years, biofilm mediated biomimetic nano-drug system (BNDDS) has become research hotspot focus in field life sciences. This new platform uses bio-nanotechnology to encapsulate synthetic NPswithin membrane, organically integrating immunogenicity, toxicity, tumor good adjustability versatility nanocarrier, shows promising applications precision therapy. this review, we systematically summarize progress BNDDS used for optimizing delivery, providing theoretical reference designing safe efficient treatment strategies improve outcomes. Keywords: nanoparticles, cell targeted therapy

Language: Английский

Citations

37
ATP‐Responsive Manganese‐Based Bacterial Materials Synergistically Activate the cGAS‐STING Pathway for Tumor Immunotherapy DOI
Yang Huang, Sisi Yang,

Quanshi Guo

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(23)

Published: Feb. 28, 2024

Abstract Stimulating the cyclic guanosine monophophate(GMP)‐adenosine monophosphate (AMP) synthase (cGAS)‐stimulator of interferon genes (STING) pathway is a crucial strategy by which bacteria activate tumor immune system. However, limited stimulation capability poses significant challenges in advancing bacterial immunotherapy. Here, an adenosine 5′‐triphosphate (ATP)‐responsive manganese (Mn)‐based material ( E. coli @PDMC‐PEG (polyethylene glycol)) engineered successfully, exhibits exceptional ability to synergistically cGAS‐STING pathway. In microenvironment, characterized elevated ATP levels, this biohybrid degrades, resulting release divalent ions (Mn 2+ ) and subsequent exposure. This combination activates pathway, as Mn enhances sensitivity cGAS extracellular DNA (eDNA) secreted bacteria. The results vivo experiments demonstrate that materials VNP20009@PDMC‐PEG effectively inhibit growth subcutaneous melanoma mice situ liver cancer rabbits. Valuable insights for development bacteria‐based immunotherapy are provided here.

Language: Английский

Citations

33
Decomposable Nanoagonists Enable NIR‐Elicited cGAS‐STING Activation for Tandem‐Amplified Photodynamic‐Metalloimmunotherapy DOI

Xun Guo,

Peng Tu,

Xiaoting Wang

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 14, 2024

Activation of the cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway has emerged as an efficient strategy to improve therapeutic outcomes immunotherapy. However, "constantly active" mode current STING agonist delivery strategies typically leads off-target toxicity and hyperimmunity. To address this critical issue, herein a metal-organic frameworks-based nanoagonist (DZ@A7) featuring tumor-specific near-infrared (NIR) light-enhanced decomposition is constructed for precisely localized activation photodynamic-metalloimmunotherapy. The engineered enabled generation mitochondria-targeted reactive oxygen species under NIR irradiation specifically release mitochondrial DNA (mtDNA) inhibit repair nuclear via hypoxia-responsive drugs. Oxidized tumor mtDNA serves endogenous danger-associated molecular pattern that activates cGAS-STING pathway. Concurrently, NIR-accelerated zinc ions overloading in cancer cells further enhance cGAS enzymatic activity through metalloimmune effects. By combining synergistically enhanced triggered by irradiation, facilitated maturation dendritic infiltration cytotoxic T lymphocytes primary eradication, which also established long-term anti-tumor immunity suppress metastasis. Therefore, developed NIR-triggered, agonist-free, tandem-amplified pathway, thereby offering distinct paradigm

Language: Английский

Citations

28
Metal‐based smart nanosystems in cancer immunotherapy DOI Creative Commons
Ying Luo,

Xiaojing He,

Qianying Du

et al.

Exploration, Journal Year: 2024, Volume and Issue: 4(6)

Published: March 22, 2024

Abstract Metals are an emerging topic in cancer immunotherapy that have shown great potential modulating immunity cycle and promoting antitumor by activating the intrinsic immunostimulatory mechanisms which been identified recent years. The main challenge of metal‐assisted lies fact free metals as ion forms easily cleared during circulation, even cause systemic metal toxicity due to off‐target effects. With rapid development nanomedicine, metal‐based smart nanosystems (MSNs) with unique controllable structure become one most promising delivery carriers solve issue, owing their various endogenous/external stimuli‐responsiveness release ions for metalloimmunotherapy. In this review, state‐of‐the‐art research progress metal‐related is comprehensively summarized. First, mainstream MSNs‐assisted will be delineated. immunological effects certain categorization MSNs different characters compositions then provided, followed representative exemplar applications treatment, synergistic combination immunotherapy. Finally, we conclude review a summary remaining challenges associated provide authors' perspective on further advances.

Language: Английский

Citations

25
Spermine delivered by ZIF90 nanoparticles alleviates atherosclerosis by targeted inhibition of macrophage ferroptosis in plaque DOI Creative Commons
Yuwu Chen,

Biyi Xu,

Quan Lin

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 4, 2025

Nowadays, emerging evidence have suggested that the ferroptosis of macrophages could contribute to progression atherosclerosis (AS). Meanwhile, Spermine (Sp) serve as an endogenous small molecule exhibiting a wide range cardiovascular protective effects. Zeolitic imidazolate framework-90 (ZIF90) nanoparticles were synthesized and utilized create novel delivery nanosystem encapsulated with Sp (CD16/32-ZIF90@Sp). The efficacy CD16/32-ZIF90@Sp in protecting against AS was evaluated ApoE-/- mice macrophages, focus on assessing potential adverse effects vivo. exhibited reliable stable within acidic environments ATP sensitivity. effectively reduced cytotoxicity Sp. As is evidenced by vitro vivo experiments, showed precise targeting atherosclerotic plaques ox-LDL-activated macrophages. Furthermore, treatment attenuated macrophage plaque without causing significant side Mechanistically, we found inhibited via improving mitochondrial function upregulating expression level GPX4/xCT. Our study demonstrated CD16/32-modified ZIF90 target plaques, leading inhibition mice. These attributed enhancement ferroptosis, limited

Language: Английский

Citations

2
An Integrated Polymeric mRNA Vaccine without Inflammation Side Effects for Cellular Immunity Mediated Cancer Therapy DOI
Pei Huang,

Lingsheng Jiang,

Hui Pan

et al.

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(3)

Published: Nov. 3, 2022

Among the few available mRNA delivery vehicles, lipid nanoparticles (LNPs) are most clinically advanced but they require cumbersome four components and suffer from inflammation-related side effects that should be minimized for safety. Yet, a certain level of proinflammatory responses innate immune activation required to evoke T-cell immunity cancer vaccination. To address these issues develop potent yet low-inflammatory vaccine vectors, series alternating copolymers "PHTA" featured with ortho-hydroxy tertiary amine (HTA) repeating units is synthesized, which can play triple roles condensing mRNA, enhancing polymeric nanoparticle (PNP) stability, prolonging circulation time. Unlike LNPs exhibiting high levels inflammation, PHTA-based PNPs show negligible inflammatory in vivo. Importantly, top candidate PHTA-C18 enables successful vivo leads robust CD8+ T cell mediated antitumor cellular immunity. Such integrated PNP provides potential approach establishing vaccines good safety profiles.

Language: Английский

Citations

57