Multi-level ROS regulation to activate innate and adaptive immune therapies
•VGRM integrated GOx and CRISPR/Cas9 on 2D vanadium carbide MXene for enhanced ROS and immune activation.•VGRM amplified ROS production and depleted GSH via cascade reaction, enhancing tumor cell damage.•VGRM activated cGAS/STING pathway, induced ICD, promoted CD8+ T cell infiltration, and reversed...
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| Published in | Chemical engineering journal (Lausanne, Switzerland : 1996) Vol. 515; p. 163429 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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Elsevier B.V
01.07.2025
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| Abstract | •VGRM integrated GOx and CRISPR/Cas9 on 2D vanadium carbide MXene for enhanced ROS and immune activation.•VGRM amplified ROS production and depleted GSH via cascade reaction, enhancing tumor cell damage.•VGRM activated cGAS/STING pathway, induced ICD, promoted CD8+ T cell infiltration, and reversed immunosuppression.•VGRM had excellent NIR-II photothermal performance for photoacoustic imaging and photothermal therapy.•VGRM inhibited tumor growth, recurrence and metastasis via ROS, photothermal, and immune activation.
Reprogramming the immunosuppressive tumor microenvironment (TME) to boost CD8+ T cell infiltration is crucial for anti-tumor immunotherapy. In this study, a bionic nanoplatform (VGRM) based on a two-dimensional vanadium carbide (MXene) carrying glucose oxidase (GOx) and CRISPR/Cas9 was constructed, which enabled a cascade reaction that amplified the generation of reactive oxygen species (ROS) while depleting glutathione (GSH) by combining MXenzyme and natural enzymes. The CRISPR/Cas9 system could reduce the expression of MTH1, depress tumor cells’ self-defense against oxidative stress and thus significantly enhance the therapeutic effect of ROS. Additionally, the excellent NIR-II photothermal performance endowed VGRM with photoacoustic imaging (PA) and photothermal therapy (PTT) capabilities. The enhanced oxidative stress and photothermal killing ability could activate the cGAS/STING innate immune pathway, induce immunogenic cell death (ICD), and at the same time reverse the immunosuppressive TME, which promoted CD8+ T cells infiltration, and thereby inhibiting tumor proliferation. Meanwhile, antigen-activated memory T cells (adaptive immunity) could suppress tumor recurrence and metastasis effectively. This study provides a novel strategy for the combined application of MXene and gene editing therapy in modulating the tumor immune microenvironment. |
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| AbstractList | •VGRM integrated GOx and CRISPR/Cas9 on 2D vanadium carbide MXene for enhanced ROS and immune activation.•VGRM amplified ROS production and depleted GSH via cascade reaction, enhancing tumor cell damage.•VGRM activated cGAS/STING pathway, induced ICD, promoted CD8+ T cell infiltration, and reversed immunosuppression.•VGRM had excellent NIR-II photothermal performance for photoacoustic imaging and photothermal therapy.•VGRM inhibited tumor growth, recurrence and metastasis via ROS, photothermal, and immune activation.
Reprogramming the immunosuppressive tumor microenvironment (TME) to boost CD8+ T cell infiltration is crucial for anti-tumor immunotherapy. In this study, a bionic nanoplatform (VGRM) based on a two-dimensional vanadium carbide (MXene) carrying glucose oxidase (GOx) and CRISPR/Cas9 was constructed, which enabled a cascade reaction that amplified the generation of reactive oxygen species (ROS) while depleting glutathione (GSH) by combining MXenzyme and natural enzymes. The CRISPR/Cas9 system could reduce the expression of MTH1, depress tumor cells’ self-defense against oxidative stress and thus significantly enhance the therapeutic effect of ROS. Additionally, the excellent NIR-II photothermal performance endowed VGRM with photoacoustic imaging (PA) and photothermal therapy (PTT) capabilities. The enhanced oxidative stress and photothermal killing ability could activate the cGAS/STING innate immune pathway, induce immunogenic cell death (ICD), and at the same time reverse the immunosuppressive TME, which promoted CD8+ T cells infiltration, and thereby inhibiting tumor proliferation. Meanwhile, antigen-activated memory T cells (adaptive immunity) could suppress tumor recurrence and metastasis effectively. This study provides a novel strategy for the combined application of MXene and gene editing therapy in modulating the tumor immune microenvironment. |
| ArticleNumber | 163429 |
| Author | Feng, Ke-Ke Xiong, Rui Li, Cheng-Lei Shao, Jing-Wei Tian, Shi-Cheng Tu, Yi-Fan Sa, Bai-Sheng |
| Author_xml | – sequence: 1 givenname: Ke-Ke surname: Feng fullname: Feng, Ke-Ke organization: Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China – sequence: 2 givenname: Cheng-Lei surname: Li fullname: Li, Cheng-Lei organization: Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China – sequence: 3 givenname: Yi-Fan surname: Tu fullname: Tu, Yi-Fan organization: Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China – sequence: 4 givenname: Shi-Cheng surname: Tian fullname: Tian, Shi-Cheng organization: Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China – sequence: 5 givenname: Rui surname: Xiong fullname: Xiong, Rui organization: Key Laboratory of Eco-materials Advanced Technology, College of Materials Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China – sequence: 6 givenname: Bai-Sheng surname: Sa fullname: Sa, Bai-Sheng organization: Key Laboratory of Eco-materials Advanced Technology, College of Materials Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China – sequence: 7 givenname: Jing-Wei surname: Shao fullname: Shao, Jing-Wei email: shaojw12@163.com organization: Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China |
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| Keywords | Tumor immune microenvironment Adaptive immunity CRISPR/Cas9 Theranostics MXene cGAS/STING |
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