ACS Nano
·
2025
·
IF 16
Si-Min Zeng,Wen-Qiang Qu,Yu-Liang Sun,Ke-Wei Chen,Kai Zhao,Jian-Hua Yan,Cheng Zhang,Chun-Xiao Liang,Yu Chen,Ting Pan,Aixi Yu,Xian-Zheng Zhang
Hypoxia-related adenosine (Ado) exerts an immunosuppressive effect in tumors by binding to the metabolic checkpoint Ado A2A receptors (A2AR), thereby hindering the activation of antitumor immunity induced by immunogenic cell death (ICD). In this study, a MnO2-assisted photosynthetic bacteria (PSB) biohybrid (MnO2@PSB) is developed to enhance tumor photothermal immunotherapy by interfering with the Ado-A2AR metabolic pathway. Specifically, manganese dioxide (MnO2) nanoflowers are conjugated onto PSB by the carbodiimide reaction to construct the biohybrid MnO2@PSB. As a photothermal agent, MnO2@PSB generates heat to “burn” tumor cells under 808 nm laser irradiation, inducing tumor cell ICD. Meanwhile, MnO2@PSB catalyzes the decomposition of endogenous hydrogen peroxide into oxygen to alleviate tumor hypoxia, thereby reducing Ado production and downregulating the expression of A2AR, further reversing the tumor immunosuppressive microenvironment and amplifying the ICD effects. In various mouse 4T1 tumor models, MnO2@PSB can enhance antitumor immune responses, prolong mouse survival, and significantly inhibit tumor growth, recurrence, and metastasis under 808 nm laser irradiation. Collectively, this study provides a direction for enhanced antitumor immunotherapy through regulating metabolic pathways.
研究领域:
肿瘤学
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免疫治疗
·
代谢通路调控
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yuetao Zhao,Zuozhong Xie,Yiyi Deng,Aji Huang,Yilang He,Bin Wen,Xiaoxiao Liao,Ruimin Chang,Guanxiong Zhang,Lin Zhu,Yanpeng Wang,Tan Li,Yanqing Zhong,Jun Zuo,Hailun Zhang,Miao Chen,Jing Liu,Xiang Chen,Hong Liu
Immunotherapy has partly achieved striking outcomes in the clinic for specific tumors. However, the responses are still limited for tumors that have restricted filtration and decreased activity of cytotoxic T cells due to the tumor stroma physical obstacles and immune-suppressive factors. Here we report an effective synergistic strategy for tumor therapy via integrating photothermal therapy and blockade of metabolic immune pathway adenosine based on a novel black phosphorus nanobomb. By rational conjugation of adenosine A2A receptor inhibitor SCH442416 (SCH) and targeting aptamer AS1411 (Apt) on black phosphorus nanosheets (BPs), we fabricate an immunostimulant nanobomb [email protected] @BPs. [email protected] @BPs shows good targeting and accumulation in melanoma. By synergism of photothermia and adenosine blockade, [email protected] @BPs could not only directly ablate tumor cells, but also boost maturation of dendritic cells, inhibit the regulatory T cells, stimulate the cytotoxic T cells, and elicit their filtration by attenuating tumor stromal barriers (e. g., cancer-associated fibroblasts and collagen). This synergistical therapy efficiently suppresses the growth of melanoma, and might be potential for other solid tumors.
研究领域:
肿瘤学
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纳米技术
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免疫疗法
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 21
·2101222
·
IF 9.933
Peng Yan,Yang Luo,Xinyang Li,Yingmin Li,Yi Wang,Jian Wu,Shaobing Zhou
In situ vaccination can trigger an antitumor immune response. However, the therapeutic effect is still limited since the high expression of adenosine binding to G protein-coupled receptor A2AR induces an immunosuppressive effect. In this work, a new formulation is presented with the combination of a nanovaccine based on redox-responsive polymer micelles and A2AR antagonist SCH58261. The micelles simultaneously encapsulate immunogenic cell death (ICD) inducer doxorubicin (DOX) and adjuvant toll-like receptor 7 and 8 (TLR7/8) agonist R848, acting as the potent in situ vaccines. A high concentration of glutathione in tumor cells leads to the disintegration of these micelles, releasing DOX and R848 to mediate ICD, inducing the activation of dendritic cells and initiating an immune response. Meanwhile, A2AR antagonist SCH58261, a generation immune checkpoint blocker, inhibits the immunosuppressive adenosinergic pathway in the tumor microenvironment, activating natural killer (NK) cells and CD8 + T cells, and inhibiting the proliferation of regulatory T cells. Therefore, this formulation can trigger a robust systemic antitumor immune response.
研究领域:
癌症研究
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免疫学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）