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
·
免疫治疗
·
代谢通路调控
·
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
·
纳米技术
·
免疫疗法
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 14
·2104182
·
IF 17.521
Yiqiong Liu,Ying Liu,Dailin Xu,Jie Zang,Xiao Zheng,Yuge Zhao,Yan Li,Ruiqing He,Shuangrong Ruan,Haiqing Dong,Jingjing Gu,Yan Yang,Qian Cheng,Yongyong Li
The metabolite adenosine plays an important immunosuppressive role in the tumor microenvironment (TME) through its ligation with the metabolic checkpoint adenosine 2A receptor (A2AR). Here, an adenosine-A2AR negative feedback pathway is highlighted during photothermal-induced immunogenic cell death (ICD). Adenosine, hydrolyzed from ATP, is amplified during the photothermal-induced ICD process. It is possible to achieve a robust ICD-based immunotherapy via targeting the adenosine-A2AR metabolic pathway. In this regard, an A2AR inhibitor-loaded polydopamine nanocarrier masked by an acid-sensitive PEG shell is designed to enable tumor-specific delivery and photothermal-induced ICD simultaneously. Upon reaching the acidic TME, the PEG shell selectively detaches and exposes the adhesive polydopamine layer, causing the inhibitors to accumulate at the tumor tissue. The accumulated inhibitors attenuate adenosine's metabolically suppressive effect and strengthen the ICD immune response. It occurs through promoting dendritic cell (DC) activation, increasing CD8 + T lymphocyte infiltration, and reducing the myeloid-derived suppressor cell (MDSC) population. Furthermore, this synergistic therapy significantly regresses the primary tumor, inhibits distal tumor growth, and prevents lung metastasis. The study highlights a strategy to enhance the immunotherapy efficacy of ICD by blocking the metabolic checkpoint A2AR using advanced nanomaterials.
研究领域:
癌症生物学
·
纳米技术
·
免疫学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2016
·
IF 3.146
Ke Li,Xia Gong,Ge Kuang,Rong Jiang,Jingyuan Wan,Bin Wang
Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. Here, we examine whether sesamin attenuates renal IRI in an animal model and explore the underlying mechanisms. Male mice were subjected to right renal ischemia for 30 min followed by reperfusion for 24 h with sesamin (100 mg/kg) during which the left kidney was removed. Renal damage and function were assessed subsequently. The results showed that sesamin reduced kidney ischemia reperfusion injury, as assessed by decreased serum creatinine (Scr) and Blood urea nitrogen (BUN), alleviated tubular damage and apoptosis. In addition, sesamin inhibited neutrophils infiltration and pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β production in IR-preformed kidney. Notably, sesamin promoted the expression of CD39, A2A adenosine receptor (A2AAR), and A2BAR mRNA and protein as well as adenosine production. Furthermore, CD39 inhibitor or A2AR antagonist abolished partly the protection of sesamin in kidney IRI. In conclusion, sesamin could effectively protect kidney from IRI by inhibiting inflammatory responses, which might be associated with promoting the adenosine-CD39-A2AR signaling pathway.
研究领域:
药理学
·
肾病学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Xudong Wen,Xiang Xiong,Guang Yang,Wenjing Xiao,Jun Hou,Tao Pan,Yonghe Hu,Shaobing Zhou
Immunotherapy has achieved remarkable research outcomes and shows the potential to cure cancer. However, its therapeutic response is limited in terms of the immunosuppressive tumor microenvironment induced by hypoxia , in which the adenosinergic A2A receptor (A2AR) pathway is mainly participated. Here, we developed a novel core/shell structured nanoplatform composed of macrophage membrane-coated mesoporous silica nanoparticles which loaded catalase , doxorubicin (Dox), and resiquimod (R848), to promote the efficacy of immunotherapy. The nanoplatform is able to actively target the tumor site via ligand binding, and the A2AR of T regulatory (Treg) cells can further be blocked due to in situ oxygen production by hydrogen peroxide catalysis. Meanwhile, Dox and R848 released from the nanoplatform can induce immunogenic cell death and enhance the activation of dendritic cells (DCs), respectively. Thus, the improved microenvironment by A2AR blockade and the stimulation of the DCs to enhance the CD8 + T cells mediated immune response were achieved. Consequently, the expression of Treg cells decreased to 9.79% in tumor tissue and the inhibition rate of tumor growth reached 73.58%. Therefore, this nanoplatform provides a potential strategy for clinical application in cancer immunotherapy.
研究领域:
癌症免疫疗法
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
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
·
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）