ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Renchuan Liang,Feng Lin,Xuezhong Mo,Jie Long,Weizhong Tang,Tao Luo,Yunxi Huang
The susceptibility of colorectal cancer (CRC) cells to Fusobacterium nucleatum (F. nucleatum) infection pose significant challenges to CRC treatment and prevention. This study addresses these challenges by mobilizing cGAS/STING axis activation and F. nucleatum-specific targeting, thereby achieving a multimodal treatment strategy for reversing the immunosuppressive microenvironment (ITM) and achieving targeted anti-F. nucleatum therapy. Specifically, a hybrid nanoplatform CuPpIX@HM was engineered using Escherichia coli and tumor cell membranes encapsulating ultrasound (US) stimulation-responsive copper protoporphyrin IX (CuPpIX). This design enables the precise accumulation of the nanoplatform at tumor sites following oral administration. Notably, upon US activation, CuPpIX generates a high level of reactive oxygen species (ROS), selectively eradicating F. nucleatum and exerting potent antitumor effects. Meanwhile, bacterial membrane components activate the cGAS/STING signaling pathway, effectively reversing the ITM, enhancing systemic antitumor immunity. Importantly, CuPpIX@HM exerts minimal disruption to healthy intestinal microbiota and remarkably increases the level of probiotics. In both orthotopic and liver metastasis, CRC models demonstrated that this strategy could significantly inhibit tumor growth and metastasis. Collectively, our study presents a highly targeted multimodal nanotherapy that holds strong potential to improve CRC treatment outcomes through the precision modulation of F. nucleatum and immune activation.
研究领域:
纳米医学
·
免疫治疗
·
微生物学
·
肿瘤学
·
生物工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Lei Diao,Yang Ma,Liping Wang,Peng Li,Bin Zhang,Weijing Meng,Jingzeng Cai,Yan Meng,Yuxun Zhou,Jingying Zhai,Huijie Chen
Thiacloprid (THI) is a synthetic insecticide, the misuse is targeted chiefly to control aphid pest species in orchards and vegetables. Melatonin (MET) is a hormone that plays crucial physiological roles in anti-inflammatory capacities of fish. We explored the function of MET (100 μM) to mitigate the toxicity induced by THI (20 μM) in lymphocytes. Our results indicate that THI led to a notable rise in lymphocyte mortality. Lymphocytes exposed to THI exhibited a heightened incidence of pyroptosis, accompanied by upregulation in expression associated with pyroptosis (NLRP3, GSDMEA, and IL-18). Meanwhile, THI exposure led to a decrease in lymphocyte mitochondrial membrane potential, an increase in mtROS levels, and a reduction in intracellular ATP, DNA, and NADPH/NADP+ levels, indicating an imbalance in the mitochondrial metabolism within the lymphocytes. Additionally, these effects were reversed by MET treatment, where MitoQ treatment showed that the suppression of mtROS reduced the lymphocyte pyroptosis caused by THI via the mtROS/cGAS-STING/NF-κB axis. Importantly, MET provided defense against the immunotoxic impacts of THI by ameliorating pyroptosis and enhancing anti-inflammatory capability via the mtROS/cGAS-STING/NF-κB axis. Our research potentiates the safeguarding of cultured fish from biological hazards caused by THI and highlights the valuable application of MET in common carp.
研究领域:
鱼类生理学
·
环境毒理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Shufen Zhang,Yingping Zeng,Kai Wang,Guangtao Song,Yiru Yu,Tingting Meng,Hong Yuan,Fuqiang Hu
Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway is an essential DNA-sensing pathway to regulate the innate and adaptive immune response, which plays an important role in tumor immunotherapy. Although the STING agonists can be used, they are limited by their inability to target immune cells and systemic immunotoxicity, calling for novel strategies to accurately and effectively activate the cGAS-STING signaling pathway. Herein, mannose-modified stearic acid-grafted chitosan (M-CS-SA) micelles with the ability to activate the cGAS-STING signaling pathway and absorb tumor antigens were constructed. The chitosan-based nano-micelles showed valid dendritic cell (DCs) targeting and could escape from lysosomes leading to the activation of the cGAS-STING signaling pathway and the maturation of DCs. In addition, a combinatorial therapy was presented based on the programmed administration of oxaliplatin and M-CS-SA. M-CS-SA adsorbed tumor antigens released by chemotherapy to construct an autologous tumor vaccine and built a comprehensive antitumor immune response. In vivo , the combinatorial therapy achieved a tumor inhibition rate of 76.31 % at the oxaliplatin dose of 5 mg/kg and M-CS-SA dose of 15 mg/kg, and increased the CD3 + CD8 + T cell infiltration. This work demonstrated that M-CS-SA and its co-treatment with oxaliplatin showed great potential in tumor immunotherapy.
研究领域:
药学
·
免疫学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-22
·
IF 17.694
Wang Xuan,Liu Yingqi,Xue Chencheng,Hu Yan,Zhao Yuanyuan,Cai Kaiyong,Li Menghuan,Luo Zhong
cGAS-STING pathway is a key DNA-sensing machinery and emerges as a promising target to overcome the immunoresistance of solid tumors. Here we describe a bovine serum albumin (BSA)/ferritin-based nanoagonist incorporating manganese (II) ions and β-lapachone, which cooperatively activates cGAS-STING signaling in dendritic cells (DCs) to elicit robust adaptive antitumor immunity. Mn 2+ -anchored mannose-modified BSAs and β-lapachone-loaded ferritins are crosslinked to afford bioresponsive protein nanoassemblies, which dissociate into monodispersive protein units in acidic perivascular tumor microenvironment (TME), thus enabling enhanced tumor penetration and spatiotemporally controlled Mn 2+ and β-lapachone delivery to DCs and tumor cells, respectively. β-lapachone causes immunogenic tumor cell apoptosis and releases abundant dsDNA into TME, while Mn 2+ enhances the sensitivity of cGAS to dsDNA and augments STING signaling to trigger downstream immunostimulatory signals. The cGAS-STING nanoagonist enhances the tumor-specific T cell-mediated immune response against poorly immunogenic solid tumors in vivo, offering a robust approach for immunotherapy in the clinics.
研究领域:
免疫学
·
肿瘤学
·
纳米技术
·
药学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2023
·
IF 8.8
Zhiqiang Zhang,Li Wang,Xia Ma,Hui Wang
A series of biodegradable nanoparticle-based drug delivery systems have been designed utilizing poly(β-amino ester)-guanidine-phenylboronic acid (PBAE-G) polymers. In this study, a novel Lentinan-Functionalized PBAE-G-nanodiamond system was developed to carry ovalbumin (LNT-PBAE-G-ND@OVA). The impact of this drug delivery system on the activation and maturation of macrophages was then assessed. Furthermore, LNT-PBAE-G-ND@OVA induced potent antibody response and showed no obvious toxicity in vitro and in vivo . Moreover, treatment with LNT-PBAE-G-ND@OVA was sufficient to alter the expression of genes associated with the cGAS-STING pathway, and the LNT-PBAE-G-ND@OVA induced upregulation of costimulatory molecules. LNT-PBAE-G-ND@OVA treatment was sufficient to induce macrophage activation through a complex mechanism in which cGAS-STING signaling plays an integral role.
研究领域:
纳米技术
·
免疫学
·
药学
·
分子生物学
✓ 已验证
DOI
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Kun Shang,Dongsheng Tang,Minhui Cui,Hongyi Hou,Bing Xiao,Jinjian Liu,Ruoshi Zhang,Rui Kuai,Jianfeng Liu,Haihua Xiao,Fan Huang,Jianliu Wang
Cisplatin is a first-line, broad-spectrum anti-tumor drug used to treat various types of cancer. However, immune-suppressive tumor microenvironments (TME) are often induced by cisplatin. Here, a first synthetic high-density lipoprotein (sHDL) nanodisc, referred as sHDL@Pt, is engineered to load a Pt(IV) prodrug (C2-Pt(IV)-C12), inducing a 2.2-fold increase in dsDNA release compared to cisplatin. This further activates the innate immune system through the cGAS-STING pathway. Using near-infrared II fluorescence imaging and single photon emission computed tomography imaging technology, it is found that sHDL@Pt can be effectively accumulated in tumor sites. The sHDL@Pt can induce severe DNA damage, which subsequently results in a more pronounced activation of the cGAS-STING pathway, further promoting dendritic cell maturation and T cell proliferation, triggering strong cytotoxic T lymphocyte responses, and inhibiting tumor growth. This work introduces a novel approach for delivering Pt(IV) prodrug that effectively initiates and activates innate immunity through the activation of the cGAS-STING pathway.
研究领域:
纳米医学
·
肿瘤学
·
免疫治疗
·
药理学
·
生物工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Yixing Huang,Xiao Li,Shengfeng Xu,Dan Zu,Haidong Liu,Hanyi He,Qimei Bao,Yanhua He,Chen Liang,Yin Shi,Xiangdong Cheng,Yaoshu Teng,Zu Ye
Nanoplastics (NPs), which are characterized by plastic particles smaller than one micrometer, have emerged as pervasive environmental pollutants, raising concerns about their potential toxicity to living organisms. Numerous investigations have highlighted the tendency of NPs to accumulate in organs, resulting in toxic effects. Despite polyvinyl chloride (PVC) being one of the most prevalent NPs, its impact on the esophagus and the associated underlying mechanisms remain largely unknown. In this study, we investigated the impact of PVC NPs on the esophagus and found that PVC NPs exposure induces oxidative stress and elicits DNA damage responses. Further analysis revealed that PVC NPs inhibit the homology-directed repair (HDR) pathway by suppressing the expression of breast cancer susceptibility gene 2 ( BRCA2 ) and growth factor receptor-bound protein 2 ( GRB2 ), resulting in genomic instability. Additionally, the release of free DNA activates cGAS-STING and the downstream NF-κB signaling, elevating inflammatory factors and chemokines, which further leads to cellular senescence. In vivo experiments corroborated these findings, showing that PVC NPs induced oxidative stress, inflammation, and cellular senescence, subsequently impacting mouse behavior. This study contributes novel insights into the health risks associated with PVC NPs exposure and identifies potential therapeutic targets.
研究领域:
毒理学
·
分子生物学
·
细胞生物学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aggregate
·
2024
·
IF 13.9
Aihui Wang,Liqun Li,Liqian Zheng,Bang-Ping Jiang,Yihao Liu,Rimei Huang,Huimin Qiu,Shichen Ji,Hong Liang,Xing-Can Shen
Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity and excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme-nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme-based hydrogels. In particular, divalent anions are found to universally drive LZF for the aggregation and transformation into three-dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near-infrared light-mediated photothermal characteristics are endowed with LZF to enhance its inhibitory activity of multidrug-resistant bacteria by the skeleton modification with genipin to produce genipin-conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO 4 -crosslinked GLZF hydrogel is constructed to sensitize the cGAS-STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the anti-recurrence of diabetic wound infection via photo-enhanced bacterial killing and the cGAS-STING pathway. Thereby, it paves the way to employ the universal divalent anion-mediated gelation strategy for the future development of functional inorganic salt hybrid lysozyme hydrogels.
研究领域:
材料科学
·
生物材料
·
生物医学工程
·
免疫学
·
伤口愈合
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Xueqin Zhu,Xiaoxi Wang,Zimai Liu,Bing Jiang,Zonghong He,Sijia Liu,Yahong Wu,Zixian Wu,Tiantian Zhang,Meiyi Liu,Kai Li,Xiaoshuang Niu,Yanfeng Gao
Although numerous peroxidase (POD)-like nanozymes have been designed for catalytic therapy of cancer, development of nanozymes with higher therapeutic efficacy and less adverse effects are challengeable. More importantly, the underlying antitumor mechanism remains largely unknown which hinders their application. Here, the nitrogen-doped carbon nanozyme (N-PCNS) as a model is utilized and demonstrated that its capacity to specifically activate the STING pathway in tumor cells through reactive oxgen species (ROS)-mediated mitochondrial DNA (mtDNA) release, which provides the initial signals for STING-dependent innate immune response. Further, a peptide-nanozyme conjugate (PNEC, OPBP1-N-PCNS), comprising a PD-L1 blocking/targeting dual-functional peptide and a cationic-coated N-PCNS is constructed, which are conjugated through a matrix metalloproteinase responsive peptide linker. The cleaved derivate nanozyme with positive charge exhibits recyclable capacity and superior ability in capturing and enhancing the transcellular transport of tumor-derived mtDNA toward DCs, thereby amplifying the STING signaling-mediated anti-tumor immune response. This study proposed a unique mechanism and design strategy for POD-like nanozyme in cancer immunotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Yuxuan Peng,Shuang Liang,Dan Liu,Kongshuo Ma,Kaiqing Yun,Mengli Zhou,Linna Hai,Mengdi Xu,Yiyang Chen,Zhaohui Wang
The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed for potent anti-tumor immunity by reversing TME. Mn-LDH is synthesized via a one-step hydrothermal method. In addition to the inherent proton neutralization capacity of LDH, the introduction of manganese oxide endows LDH with an additional ability to produce oxygen. Mn-LDH effectively releases Mn 2+ and Mg 2+ upon exposure to TME with high levels of H + and H 2 O 2 , which activates synthase-stimulator of interferon genes pathway and maintains the cytotoxicity of CD8 + T cells respectively, achieving a cascade-like role in innate and adaptive immunity. The locally administered Mn-LDH facilitated a “hot” network consisting of mature dendritic cells, M1-phenotype macrophages, as well as cytotoxic and helper T cells, significantly inhibiting the growth of primary and distal tumors. Moreover, the photothermal conversion capacity of Mn-LDH sparks more robust therapeutic effects in large established tumor models with a single administration and irradiation. Overall, this study guides the rational design of TME-modulating immunotherapeutics for robust immune activation, providing a clinical candidate for next-generation cancer immunotherapy.
研究领域:
癌症免疫学
·
纳米技术
·
治疗开发
·
免疫治疗
·
肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Kaiyuan Liu,Pengfei Zan,Zihua Li,Hengli Lu,Peng Liu,Li Zhang,Hongsheng Wang,Xiaojun Ma,Feng Chen,Jing Zhao,Wei Sun
The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here we present a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable systemic antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study offers a comprehensive approach to treat OS by mild photothermal therapy and modulating the immune microenvironment, exhibiting considerable potential in addressing the constraints associated with current therapeutic modalities. This article is protected by copyright. All rights reserved
研究领域:
癌症治疗
·
免疫学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Jie Lei,Weifeng Zhang,Liang Ma,Yaqi He,Huaizhen Liang,Xiaoguang Zhang,Gaocai Li,Xiaobo Feng,Lei Tan,Cao Yang
The therapeutic effect of cancer immunotherapy is restrained by limited patient response rate caused by ‘cold’ tumors with an intrinsically immunosuppressive tumor microenvironment (TME). Activating stimulator of interferon genes (STING) confers promising antitumor immunity even in ‘cold’ tumors, but the further promotion of STING agonists is hindered by undesirable toxicity, low specificity and lack of controllability. Herein, an ultrasound-controllable cGAS-STING amplifying nanoagonist was constructed by coordinating mitochondria-targeting ligand triphenylphosphonium (TPP) to sonodynamic cobalt organic framework nanosheets (TPP@CoTCPP). The Co ions specifically amplify STING activation only when cytosolic mitochondrial DNA leakage is caused by sonocatalysis-induced ROS production and sensed by cGAS. A series of downstream innate immune proinflammatory responses induced by local cGAS-STING pathway activation under spatiotemporal ultrasound stimulation efficiently prime the antitumor T-cell response against bone metastatic tumor, a typical immunosuppressive tumor. We also found that the coordination of TPP augments the sonodynamic effect of CoTCPP nanosheets by reducing the band gap, improving O 2 adsorption and enhancing electron transfer. Overall, our study demonstrates that the targeted and amplified cGAS-STING activation in cancer cell controlled by spatiotemporal ultrasound irradiation boosts high-efficiency sonodynamic-ionicimmunotherapy against immunosuppressive tumor.
研究领域:
癌症免疫疗法
·
纳米技术
·
生物医学工程
·
分子生物学
·
免疫学
✓ 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）