Manganese molybdate nanodots with dual amplification of STING activation for “cycle” treatment of metalloimmunotherapy

Lei, Huali; Li, Quguang; Li, Guangqiang; Wang, Tianyi; Lv, Xinjing; Pei, Zifan; Gao, Xiang; Yang, Nailin; Gong, Fei; Yang, Yuqi; Hou, Guoqing; Chen, Minjiang; Ji, Jiansong; Liu, Zhuang; Cheng, Liang

doi:10.1016/j.bioactmat.2023.07.026

Cited by 12 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to that in the control groups, the phosphorylation of STING ( p -STING) in the MCSP treatment group was significantly greater, confirming the successful activation of the STING signal by the release of Mn 2+ . The activated STING protein recruits and activates TANK-binding kinase 1 (TBK1), which leads to the phosphorylation of interferon regulatory factor 3 (IRF3) . Consequently, the levels of phosphorylated TBK1 ( p -TBK1) and phosphorylated IRF3 ( p -IRF3) were increased in the MCSP treatment group, demonstrating successful activation of the cGAS-STING pathway by MCSP treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Consequently, the levels of phosphorylated TBK1 ( p -TBK1) and phosphorylated IRF3 ( p -IRF3) were increased in the MCSP treatment group, demonstrating successful activation of the cGAS-STING pathway by MCSP treatment. Moreover, mtDNA acts as an adjuvant to further enhance the activation of cGAS-STING pathway . The H 2 S released from MCSP can damage mitochondria and release mtDNA.…”

Section: Resultsmentioning

confidence: 99%

“…The activated STING protein recruits and activates TANK-binding kinase 1 (TBK1), which leads to the phosphorylation of interferon regulatory factor 3 (IRF3). 33 Consequently, the levels of phosphorylated TBK1 (p-TBK1) and phosphorylated IRF3 (p-IRF3) were increased in the MCSP treatment group, demonstrating successful activation of the cGAS-STING pathway by MCSP treatment. Moreover, mtDNA acts as an adjuvant to further enhance the activation of cGAS-STING pathway.…”

Section: Cgas-sting Pathway Activation By Mcspmentioning

confidence: 96%

“…Moreover, mtDNA acts as an adjuvant to further enhance the activation of cGAS-STING pathway. 33 The H 2 S released from MCSP can damage mitochondria and release mtDNA. Therefore, it was anticipated that the released H 2 S would not only destroy the calcium buffer system to induce calcium overload but also amplify the effect of Mn 2+ on activating the cGAS-STING pathway by promoting mtDNA release.…”

Section: Cgas-sting Pathway Activation By Mcspmentioning

confidence: 99%

See 3 more Smart Citations

Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment

Liu,

Lei,

Hou

et al. 2024

ACS Nano

Self Cite

View full text Add to dashboard Cite

The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness of immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectively enhance the antitumor immune response of the cervical cancer through gas-amplified metalloimmunotherapy with dual activation of pyroptosis and STING pathway. The bioactive MCSP exhibited the ability to rapidly release Ca 2+ , Mn 2+ , and H 2 S in response to the tumor microenvironment. H 2 S disrupted the calcium buffer system of cancer cells by interfering with the oxidative phosphorylation pathway, leading to calcium overload-triggered pyroptosis. On the other hand, H 2 S-mediated mitochondrial dysfunction further promoted the release of mitochondrial DNA (mtDNA), enhancing the activation effect of Mn 2+ on the cGAS-STING signaling axis and thereby activating immunosuppressed dendritic cells. The released H 2 S acted as an important synergist between Mn 2+ and Ca 2+ by modulating dual signaling mechanisms to bridge innate and adaptive immune responses. The combination of MCSP NPs and PD-1 immunotherapy achieved synergistic antitumor effects and effectively inhibited tumor growth. This study reveals the potential collaboration between H 2 S gas therapy and metalloimmunotherapy and provides an idea for the design of nanoimmunomodulators for rational regulation of the immunosuppressive tumor microenvironment.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Cgas-sting Pathway Activation By Mcspmentioning

confidence: 96%

Section: Cgas-sting Pathway Activation By Mcspmentioning

confidence: 99%

See 2 more Smart Citations

Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment

Liu,

Lei,

Hou

et al. 2024

ACS Nano

Self Cite

View full text Add to dashboard Cite

show abstract

“…The cGAS-STING pathway can be activated by Mn 2+ and Zn 2+ , which implies that they possess the capacity to function as immune activators [ 101 , 102 ]. Lei et al [ 103 ] designed the bimetal oxide manganese molybdate nanoparticle MnMoO x -PEG (MMP NDs), which was constructed from Mn 2+ and MoO 4 2− and modified by distearoyl phosphatidylethanolamine-polyethylene glycol 5000 (DSPE-PEG 5k ). The presence of high-valence Mo 6+ and Mn 4+ in MMP NDs allows for their reduction into a low-valence Mo 5+ and Mn 2+ by GSH.…”

Section: Transition Metal Oxide Nanozymesmentioning

confidence: 99%

Transition-Metal-Oxide-Based Nanozymes for Antitumor Applications

Sun,

Bai,

Zhao

et al. 2024

Materials

View full text Add to dashboard Cite

Transition metal oxide (TMO)-based nanozymes have appeared as hopeful tools for antitumor applications due to their unique catalytic properties and ability to modulate the tumor microenvironment (TME). The purpose of this review is to provide an overview of the latest progress made in the field of TMO-based nanozymes, focusing on their enzymatic activities and participating metal ions. These nanozymes exhibit catalase (CAT)-, peroxidase (POD)-, superoxide dismutase (SOD)-, oxidase (OXD)-, and glutathione oxidase (GSH-OXD)-like activities, enabling them to regulate reactive oxygen species (ROS) levels and glutathione (GSH) concentrations within the TME. Widely studied transition metals in TMO-based nanozymes include Fe, Mn, Cu, Ce, and the hybrid multimetallic oxides, which are also summarized. The review highlights several innovative nanozyme designs and their multifunctional capabilities. Despite the significant progress in TMO-based nanozymes, challenges such as long-term biosafety, targeting precision, catalytic mechanisms, and theoretical supports remain to be addressed, and these are also discussed. This review contributes to the summary and understanding of the rapid development of TMO-based nanozymes, which holds great promise for advancing nanomedicine and improving cancer treatment.

show abstract

A Bioactive Injectable Hydrogel Regulates Tumor Metastasis and Wound Healing for Melanoma via NIR‐Light Triggered Hyperthermia

Liu,

Shen,

Bing

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG‐Mngel) formed by crosslinking sodium alginate (SA) with manganese‐doped bioactive glass (BG‐Mn) is developed as a versatile platform for anti‐tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS‐STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune‐suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG‐Mngel with anti‐PD‐1 antibody (α‐PD‐1) for the treatment of malignant melanoma, it shows enhanced anti‐tumor immune response and long‐term immune memory response. Remarkably, BG‐Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full‐thickness wounds. Overall, BG‐MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.

show abstract

Manganese molybdate nanodots with dual amplification of STING activation for “cycle” treatment of metalloimmunotherapy

Cited by 12 publications

References 38 publications

Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment

Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment

Transition-Metal-Oxide-Based Nanozymes for Antitumor Applications

A Bioactive Injectable Hydrogel Regulates Tumor Metastasis and Wound Healing for Melanoma via NIR‐Light Triggered Hyperthermia

Contact Info

Product

Resources

About