CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Pengyu Xue,Yinghan Wang,Xuefei Wang,Shilin Zhou,Xiaochen Wu,Lin Long,Chuanlong Guo
The incidence rate of breast cancer remains high, and lung metastasis often leads to treatment failure. Immunotherapy based on the cyclic guanosine monophosphate synthesis (cGAS) − interface gene stimulatory factor (STING) pathway is expected to bring benefits to the treatment of breast cancer. This study provided a delivery system based on fucoidan (Fu) and polyvinylpyrrolidone (PVP) for the potential molecule resveratrol (Res). The study confirmed that Fu and PVP were assembled into nanoparticles through hydrogen bonding and effectively loaded Res (Fu/PVP/Res). Interestingly, the adsorption of Zn 2+ (Fu/PVP/Res Zn 2+ ) was expected to provide impetus for the treatment of breast cancer. The results in vitro confirmed that Fu/PVP/Res Zn 2+ significantly inhibited the proliferation of breast cancer 4T1 cells, induced the accumulation of mitochondrial reactive oxygen species (ROS) and the damage of mitochondrial membrane potential (MMP), and further induced the cytoplasmic release of mtDNA, which was the direct cause of the activation of cGAS-STING pathway. In vivo studies confirmed that Fu/PVP/Res Zn 2+ treatment inhibited the growth of 4T1 transplanted tumors. Excitingly, Fu/PVP/Res Zn 2+ treatment also prevented lung metastasis of in situ tumors. The in vivo mechanism confirmed that Fu/PVP/Res Zn 2+ treatment activated the cGAS-STING pathway and induced abnormal expression of tumor apoptosis factors such as Bax/Bcl-2. In conclusion, our research provided potential for the treatment of breast cancer.
研究领域:
肿瘤学
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免疫学
·
药剂学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Shining Niu,Qian Chen,Lulu Yu,Xiao Wang,Haipeng Yu,Mei Wen,Zhigang Chen,Nuo Yu,Kun Li
Natural bacteria and bacterial bionics offer significant advantages in the synergistic approach to cancer treatments, while the development of such platforms remains challenging. Herein, bacterial membrane-coated chlorin e6-conjugated bacteriform manganese dioxide platform (BCBM) has been developed for amplifying phototherapeutic efficacy of tumors. The BCBM platform has been prepared by the in-situ growth of manganese dioxide on the surface of silica nanorods and subsequent etching process, photosensitizer conjugation, and bacterial membrane encapsulation. The manganese dioxide and bacterial membrane endow the BCBM with bacteria-like characteristics, enabling a specific response to the tumor microenvironment (TME). The manganese dioxide can react with hydrogen peroxide to produce large amounts of oxygen and manganese ions under acidic conditions. Upon near-infrared irradiation, the BCBM exhibits an excellent ability to generate reactive oxygen species because of sufficient oxygen supply. Furthermore, the released manganese ions activate cGAS-STING pathway, leading to the efficient apoptosis of cancer cells. The process of apoptosis is accompanied by the release of tumor-associated signaling molecules, which enhances therapeutic efficacy. Therefore, this work offers insights into designing biomimetic multifunctional nanoagents against cancers.
研究领域:
肿瘤学
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生物材料
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免疫治疗
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纳米医学
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产品关联
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yue Chen,Di Wu,Quan Li,Zhenghua Wei,Qian Liu,Jin Li,Daohui Gong,Chaowang Huang,Qianyi You,Hang Qian,Guansong Wang
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause severe lung inflammation and damage, compromising respiratory function. Nanomedicine offers hope in controlling this inflammation. DNA nanostructures, as drug carriers, stand out due to their non-toxic, programmable, and precisely controllable traits. However, they face challenges in physiological stability and functionalization as carriers. Here, we introduce TET AG , DNA tetrahedra assembled and functionalized with aminoguanidine without magnesium. Aminoguanidine not only aids tetrahedron assembly but also inhibits the cyclic GMP-AMP synthase and stimulator of interferon (cGAS-STING) pathway, a key inflammatory signal. By integrating STING siRNA into TET AG (TET AG -STING), we achieve synergistic anti-inflammatory effects in ALI/ARDS. Our results show that TET AG offers improved stability and cellular uptake. Importantly, TET AG -STING exhibits potent anti-inflammatory activity in vitro and in a Lipopolysaccharides-induced mouse model following intratracheal administration. This significantly improves lung injury scores and pulmonary functions. These findings underscore aminoguanidine’s therapeutic potential in ALI/ARDS and highlight the promise of DNA nanostructures in medical applications.
研究领域:
医学
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纳米医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Jingwen Xiao,Shilin Zhou,Fengshu Fei,Lin Long,Chuanlong Guo
Ulcerative colitis (UC) is a persistent intestinal disorder featuring periodic flare-ups of the colon's inner lining inflammation. Current therapeutic strategies, while effective in managing symptoms, are often limited by side effects and high costs. This study investigates the potential of pectin-loaded ferulic acid (PC-FA) nanoparticles as a novel therapeutic approach for UC, focusing on their ability to modulate the cGAS-STING pathway, a key mediator in the inflammation associated with UC. PC-FA nanoparticles were prepared and characterized for their physicochemical properties, antioxidant capacity, biocompatibility, and influence on the cGAS-STING pathway. In vitro experiments demonstrated that PC-FA nanoparticles enhanced the solubility and bioavailability of ferulic acid (FA), reduced oxidative stress, and protected colon epithelial cells from damage caused by the administration of dextran sulfate sodium (DSS). In vivo studies in a DSS-induced colitis mouse model showed that PC-FA nanoparticles mitigated weight reduction, lowered disease activity index (DAI) scores, and sustained colon length, and ameliorated histopathological changes. Additionally, PC-FA nanoparticles effectively targeted DNA damage and inhibited the cGAS-STING pathway, leading to a significant reduction in pro-inflammatory cytokines. Pharmacokinetic studies revealed rapid absorption of PC-FA in the bloodstream, with a predominant distribution in the intestines. The study concludes that PC-FA nanoparticles are a promising therapeutic strategy for UC, offering targeted drug delivery, enhanced bioavailability, and anti-inflammatory effects.
研究领域:
药理学
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免疫学
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消化系统疾病
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Shaofeng Wang,Quanwei Li,Pan Guo,Luna Su,Tingyu Liang,Wenlan Yu,Qingwen Yang,Jianying Guo,Zhaoxin Tang,Jianzhao Liao
Terbuthylazine (TBA) is a widely employed pesticide that has been found to be a significant source of food and environmental pollution. Excessive exposure to TBA raises considerable apprehension regarding its potential impact on biological health, but its underlying toxic mechanisms have not been reported. Our findings indicated that TBA exposure could cause intestinal damage , as evidenced by decrease in the quantity of cupped cells and decrease in the expression of intestinal barrier-related proteins (Claudin-1, Occludin , ZO-1, and JAM-1). Additionally, exposure to TBA resulted in a significant decrease in the expression levels of oxidative stress-related genes and proteins. Furthermore, the expression of 8-hydroxy-2′-deoxyguanosine was significantly upregulated. Additionally, excessive exposure to TBA led to a substantial release of mitochondrial DNA, which further activated the cGAS-STING pathway and caused TBK1 and IRF3 phosphorylation. Meanwhile, mitophagy was activated under TBA exposure, as evidenced by decrease in the protein and gene levels of p62 and increase in the levels of PINK1 , PARKIN and LC3 II. Therefore, our results suggested that TBA exposure induced oxidative stress in the jejunum and caused mtDNA leakage, for activating the cGAS-STING pathway, which in turn promoted mitophagy . These findings revealed the toxicity mechanisms of TBA, which provided new insights into food safety caused by pesticide contamination.
研究领域:
毒理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Yonglong Jin,Nina Dong,Shosei Shimizu,Yinuo Li,Yuan Yao,Hong Qiao,Xiguang Liu,Shuai Liu,Chuanlong Guo,Lijie Wang
The incidence rate and mortality rate of breast cancer remain high, and there is an urgent need for safe and effective drugs. The excellent biological activity of hesperidin (HE) is a potential drug for the treatment of breast cancer. In this study, silk fibroin peptides (SFP) were used as delivery carriers and HE loaded SFP nanofibers (SFP/HE NFs) was prepared. The in vitro results showed that SFP/HE NFs significantly inhibited the proliferation and migration of breast cancer cell MDA-MB-231 compared with free HE. The mechanism results demonstrated that SFP/HE NFs induced apoptosis and DNA double stranded damage (DSBs) and further activated the cyclic monophosphate guanosine adenosine monophosphate synthase- stimulator of interferon gene (cGAS-STING) pathway. The in vivo studies showed that SFP/HE NFs treatment significantly inhibited the growth of breast cancer, with an inhibition rate of 65.9 % (100 mg/kg). In vivo mechanism studies also demonstrated that the anti-tumor activity of SFP/HE NFs was related to the activation of the cGAS-STING pathway. Interestingly, we found that the combination of SFP/HE NFs and cisplatin not only enhanced the anti-tumor activity of cisplatin, but also alleviated cisplatin induced nephrotoxicity. In conclusion, our results demonstrate the benefits of activating the cGAS-STING pathway in the treatment of breast cancer, which is expected to provide potential candidates for combined treatment of breast cancer.
研究领域:
药理学
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肿瘤学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Wen E.,Tian Yu,Chen Yu,Wang Zhigang,Feng Yi,Liao Zhen
Despite the encouraging developments in tumor immunotherapy, the complex tumor microenvironment (TME) and abnormal energy metabolism persist as key factors facilitating immune escape. Recent research has emphasized the significant potential of the Manganese ions (Mn 2+ ) as a “immune ion reactors” have the potential to stimulate cGAS-STING signaling pathway in modulating tumor immunotherapy. However, their efficacy is limited by insufficient targeting and lack of tumor specificity. To address these challenges, we have developed a nano-drug named as LT@MnO@MON-HA (LMMH), which incorporates manganese oxide (MnO) nanoparticles as the core and organic mesoporous silica as the outer layer. The mitochondrial glycolysis inhibitor lonidamine (LT) is encapsulated within the mesopores of LMMH and subsequently coated with hyaluronic acid to achieve precise tumor-targeted drug delivery. After reaching the tumor site, LMMH can decompose in the reducing and acidic TME, releasing LT and Mn 2+ . Once internalized by cells, LT rapidly localizes to mitochondria via functional groups, disrupting mitochondrial metabolism and increasing intracellular reactive oxygen species levels. Mn 2+ catalyze the conversion of hydrogen peroxide (H₂O₂) into more cytotoxic hydroxyl radicals (·OH), thereby enhancing chemodynamic therapy (CDT). The mesoporous silica shell of LMMH is capable of depleting glutathione in the TME, enhancing CDT. Moreover, LMMH functions as an agonist of the cGAS-STING pathway, stimulating cytokine release and activating effector T cells, which in turn triggering systemic immune responses against primary and metastatic cancers. Collectively, these finding highlights the dual mechanisms by which LMMH enhances combination immunotherapy by regulating the TME and tumor metabolism. Graphical
研究领域:
肿瘤学
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免疫学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2025
·
IF 4.6
Hongqiao Wei,Yongxin Chen,Zhenmin Qin,Honglei Wang,Yujia Liu,Tang Song,Yong Wu,Wanxiang Hu,Xiaowei Huang,Guodong Lu,Jing Zhou
Artesunate, a derivative of artemisinin, has a variety of pharmacological effects. Its potential application in ischemic brain injury still largely unknown. This study investigated the therapeutic effect and pharmacological mechanism of artesunate in neuronal injury following cerebral ischemia, and explore the potential role of lysosomal function and cGAS-STING signaling pathway in ischemia injury and artesunate treatment. Studies in rat models have revealed that artesunate can ameliorate neuronal injury and improve learning and memory function following ischemic insults. Furthermore, both in vivo and in vitro studies have confirmed that artesunate can protect neural cells from ischemic injury-induced cell death. Mechanistically, artesunate appears to exert its neuroprotective actions by activating lysosomal function and inhibiting the cGAS-STING pathway-mediated imflammatory repsonse. Our findings provide valuable insights into the therapeutic effects of artesunate exerting a neuroprotective role in chronic ischemic brain injury by activating lysosomal function, inhibiting the cGAS-STING pathway, and regulating the inflammatory response. This study offers a potential therapeutic strategy by regulating lysosome for the treatment of stroke and related neurological disorders.
研究领域:
神经科学
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药理学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2025
·Vol. 86
·期 3
·e70090
·
IF 4.2
Cailan Wang,Xinyi Lin,Shichun Guan,Qiaoyuan Wu,Shixiong Liang
Dihydroartemisinin (DHA) is a derivative of artemisinin, which affects inflammation, oxidative stress, and immune regulation. However, the mechanism underlying its effects remains largely unknown. This study aims to explore the mechanism by which DHA affects radiation-induced lung injury (RILI), providing new insights for lung radiotherapy. To elucidate its mechanism of action, C57BL/6 J mice were irradiated with 15 Gy whole chest. RILI was evaluated by qRT-PCR, ELISA, histology, Western blot analysis, immunohistochemistry, and RILI signaling cascade studies. In addition, small interfering RNAs were employed to knockdown cGAS proteins in the cGAS-STING signaling pathway in the human bronchial epithelium cell line (BEAS-2B). Both In Vivo and Vitro experiments were conducted to investigate the specific mechanism by which DHA alleviated RILI. We observed the activation of the cGAS-STING pathway, along with the phosphorylation of the downstream target NF-κB and an increase in inflammatory factor levels in the mouse model following radiation exposure. In the cell model, irradiation also triggered the activation of the cGAS-STING signaling pathway and its downstream targets, leading to elevated levels of inflammatory factors. Notably, knocking down the cGAS using small interfering RNA in the BEAS-2B cells significantly alleviated RILI in the cell model. Our study elucidated the mechanism of DHA reducing RILI through the cGAS/STING/NF-κB signaling pathway, and revealed that the GAS/STING/NF-κB axis may be a potential therapeutic target for RILI.
研究领域:
医学
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药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Qingdong Li,Yuanyuan Cui,Zhenhong Xia,Wenjuan Gao,Jianmin Xiao,Zhen Zhao,Lei Yang,Guilong Zhang,Zhengyan Wu
Immunotherapy has emerged as a promising approach for melanoma treatment. However, the efficacy of traditional immune checkpoint inhibitors (ICIs) remains limited due to the immunosuppressive tumor microenvironment. In this study, a novel nano-immune agonist, pLCGM-OVA, was developed to induce cuproptosis and activate the cGAS-STING pathway, thereby enhancing melanoma immunotherapy. The pLCGM-OVA was synthesized by conjugating PDGFB with liposomes that encapsulate CuGdMn nanoclusters (CGM) and ovalbumin (OVA). Upon exposure to the acidic microenvironment of tumours, pLCGM-OVA undergoes degradation, releasing Cu ions, Mn ions, and free OVA. This release triggers reactive oxygen species-mediated cuproptosis and activates the cGAS-STING pathway via Mn, leading to the subsequent induction of immunogenic cell death (ICD). Simultaneously, free OVA and ICD antigens are presented to dendritic cells (DCs), promoting their maturation and enhancing cytotoxic T lymphocyte infiltration, thus improving the efficacy of tumour immunotherapy. In vitro and in vivo studies demonstrated that pLCGM-OVA significantly inhibited tumour growth and recurrence with minimal systemic toxicity, owing to the combined effects of cuproptosis and immunotherapy. Moreover, pLCGM-OVA exhibited excellent T 1 contrast (9.26 mM −1 s −1 ), significantly enhancing T 1 -weighted magnetic resonance imaging signals of tumours, facilitating accurate melanoma diagnosis. Overall, this work presents a highly promising candidate for the development of potent immune agonists for melanoma treatment.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Kunguo Liu,Shiyu Du,Jiawei Yang,Juanjuan Li,Shijie Wang,Zhibin Zhang,Wen Luo,Chao Chen,Jingjing Yang,Xin Han
The immunosuppressive tumor microenvironment (TME) in solid tumors often impedes the efficacy of immunotherapy. Bacterial outer membrane vesicles (OMVs), as a promising cancer vaccine that can potently stimulate immune responses, have garnered interest as a potential platform for cancer therapy. However, the low yield of OMVs limits their utilization. To address this limitation, we developed a novel approach to synthesize OMV-like multifunctional synthetic bacterial vesicles (SBVs) by pretreating bacteria with ampicillin and lysing them through sonication. Compared to OMVs, the yield of SBVs increased by 40 times. Additionally, the unique synthesis process of SBVs allows for the encapsulation of bacterial intracellular contents, endowing SBVs with the capability of delivering catalase (CAT) for tumor hypoxia relief and activating the host cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. To overcome the toxicity of lipopolysaccharide (LPS) on the SBVs surface, we decorated SBVs with a biocompatible polydopamine (PDA) shell, which allowed TME reprogramming using SBVs to be conducted without adverse side effects. Additionally, the photosensitizer indocyanine green (ICG) was loaded into the PDA shell to induce immunogenic cell death and further improve the efficacy of immunotherapy. In summary, the SBVs-based therapeutic platform SBV@PDA/ICG (SBV@P/I) can synergistically elicit safe and potent tumor-specific antitumor responses through combined immunotherapy and phototherapy.
研究领域:
肿瘤学
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免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 16
·8049
·
IF 13.3
Jiaorong Qu,Jianan Li,Le Wang,Yufei Li,Yinqiang Zhang,Jingtao Li,Zixuan Huo,Junsong Han,Runping Liu,Guifang Fan,Yinhao Zhang,Xiaoyong Xue,Xiaojiaoyang Li
Background and aims: Inducing the senescence of activated hepatic stellate cells (HSCs) has emerged as a promising therapeutic strategy for liver fibrosis, with potential connections to the Yes-associated protein (YAP)-controlled cGAS-STING pathway. However, the regulatory role of cytoskeletal dynamics on HSC senescence and its potential as a target for natural products have remained poorly understood. Methods: We employed preclinical in vivo and in vitro transcriptome analyses, experimental systems, Tmem173 -/- mice and liver-specific STING knockdown mice to demonstrate the anti-fibrotic effects and mechanism of ligustilide (LIG). Results: LIG selectively bound to monomeric globular actin (G-actin), thereby preventing its polymerization into polymeric filamentous actin (F-actin), which disturbed its interaction with intermediate filament component lamin A/C and initially destroyed the nuclear membrane. Moreover, the disruption of nuclear membrane caused YAP leakage from nuclear, which in turn suppressed lamin A/C and created a deleterious feedback loop that exacerbated nuclear membrane destabilization. Consequently, nuclear double stranded DNA (dsDNA) leakage caused by the above damage cascade ultimately triggered the activation of the cGAS-STING signaling pathway, promoting senescence-associated secretory phenotypes (SASPs) release and inducing HSC senescence. Moreover, the induction of HSC senescence and anti-fibrotic effects of LIG were completely abrogated in both whole-body STING knockout and liver-specific STING knockdown mice. Conclusions: By interacting with G-actin, LIG disrupted the cytoskeleton to compromise nuclear integrity with the involvement of YAP and further stimulated the cGAS-STING pathway, leading to the release of SASPs and HSC senescence, which ultimately mitigated liver fibrosis.
研究领域:
药理学
·
细胞生物学
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分子生物学
·
肝病学
·
生物化学
✓ 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）