CHEMICAL ENGINEERING JOURNAL
·
2024
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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
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药剂学
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产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-21
·
IF 12.6
Yang Yi,Guo Jiaxin,Qi Jialong,Deng Wenxia,Hu Jialin,Hasan Muhammad Waqqas,Deng Fei,Zhou You,Song Zhengji,Deng Wei,Chen Wenjie
Immune checkpoint blockade therapy (iCBT) has revolutionized cancer treatment, however, there is a low response rate, especially in treating postsurgical reoccurring tumors. Vaccine based immunotherapy can sensitize iCBT, but its development was largely hindered by inefficient delivery and high requirements of storage. In this study, the vaccine loaded with immunostimulant was employed to improve iCBT-based adjuvant postsurgical therapy. A lyophilized, antigen E7 peptide and manganese ion (Mn 2+ ) co-delivered tumor vaccine was developed based on lipid nanoparticles (EM@LNP). The vaccination efficacy was examined in both prophylactic and therapeutic schemes in murine subcutaneous models, the synergetic effect of vaccination combined with anti-PD-1 therapy was further investigated in post-operative tumor model. EM@LNP vaccination elicited effective CD8 + T cell response through modulating tumor immunosuppressive microenvironment and conferring immune memory, demonstrating potent immunization in both preventive and therapeutic schemes. What’s more, EM@LNP vaccination orchestrated with iCBT, efficiently repressing tumor recurrence. Further mechanism studies using inhibitor for cells invitro and the investigation using STING −/− mice confirmed that the cGAS-STING signaling pathway activated by Mn 2+ is indispensable for LNP vaccination and the coordination with iCBT-based adjuvant immunotherapy. In summary, this study shows a lyophilized LNP vaccine could significantly amplify iCBT efficiency, providing a translational strategy of adjuvant immunotherapy for treating postsurgical tumor recurrence. Graphical abstract
研究领域:
肿瘤学
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免疫学
·
药剂学
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生物医学工程
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产品关联
DOI
PubMed
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
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Mengzi Hu,Yaqiong Wang,Xue-Bo Yin
In addition to the robust adhesive properties, there is a pressing demand for ideal adhesives in tumor surgery that possess anti-tumor therapeutic effects. In this study, we introduce BSA-MnO 2 -GP@Ca-Y (BMGY) bio-glue by integrating bovine serum albumin (BSA)-MnO 2 , genipin (GP), and Ca-Y zeolite. Ca-Y zeolite exhibits the thrombin activity for hemostasis, while the cross-linking of BSA, GP, and skin tissue induces wound adherence upon laser irradiation for normalized skin structure within nine days. The heat generated during the “photothermal suture” process ablates residual tumor cells and produces antigen fragments, which are internalized by antigen presenting cells. The released Mn ions subsequently activate the cGAS-STING pathway, enhancing immunogenicity. Consequently, tumor-infiltrating p-TBK1 and interferon-β levels are significantly increased, ensuring robust anti-tumor immunity following BMGY treatment. Thus, BMGY bio-glue achieves hemostasis, wound bonding, ablation of residual tumor cells, and tumor recurrence inhibition, simultaneously. Beyond Ca-Y zeolite, BSA-MnO 2 -GP serves as a versatile platform for loading other drugs or active species to boost therapeutic efficacy. Therefore, we present a successful bio-glue paradigm with significant translational potential for various postsurgical management applications.
研究领域:
生物医学工程
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肿瘤免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 13
·e70688
·
IF 4.2
Li‐Ping Kang,Cong Xu,Pan Xu,Dong‐Hui Huang,Ze‐Bo Jiang
Non‐small cell lung cancer (NSCLC) stands as a predominant cause of cancer‐related mortality worldwide. Brazilin, an active isoflavonoid compound derived from Chinese herbs, has displayed anti‐cancer properties across various cancer cell lines. However, the precise anti‐tumour mechanism of Brazilin in NSCLC remains incompletely understood. In this paper, we demonstrated that Brazilin treatment significantly reduced the proliferation of NSCLC cells and induced apoptosis. Additionally, Brazilin caused G2 cell cycle arrest in NSCLC cells, characterised by decreased expression of Cyclin B1 and increased expression of P21. Brazilin also induced mitochondrial dysfunction and ROS production in NSCLC cells. Mechanistically, Brazilin treatment significantly activated the STING pathway and upregulated the expression of CXCL10, CXCL9, and CCL5 in NSCLC cell lines. Notably, the inhibition of the STING pathway with H‐151 enhances cell viability, suggesting STING is involved in Brazilin‐induced apoptosis. These findings underscore Brazilin as a promising anti‐cancer agent for NSCLC.
研究领域:
肿瘤学
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药理学
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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
JOURNAL OF NANOBIOTECHNOLOGY
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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
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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
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Huijiao Fu,Xiaoqiao Guo,Feng Fang,Cao Zhou,Yuanyuan Chen,Xuanbo Zhang,Bingchen Zhang,Xinran Li,Qiwen Liu,Jie Liu,Wei Chen,Ling Yu,Zhiqiang Yu,Xuefeng Wang
Cisplatin serves as the cornerstone medication in ovarian cancer (OC) chemotherapy; however, numerous resistance factors exist, resulting in unsatisfactory clinical treatment outcomes. Concurrently, OC frequently establishes an immunosuppressive microenvironment, which further exacerbates the challenges of cisplatin chemotherapy. Hence, it is particularly significant to explore a therapeutic approach capable of overcoming cisplatin resistance while reversing the immunosuppressive microenvironment of OC. Here, we synthesized a novel cisplatin polyprodrug (PTP) containing thioketal units, which self-assembled with a stimulator of interferon genes (STING) small-molecule agonist (SR-717) to form redox-smart-responsive PTP@SR-717 nanoparticles (NPs), enabling synergistic chemo-immunotherapy. Specifically, PTP@SR-717 NPs enhanced the anti-tumor effect of cisplatin through three key mechanisms: (i) Pre-target factors: Enhancing intracellular cisplatin uptake and reducing GSH-mediated detoxification to promote platinum accumulation. (ii) On-target factors: Utilizing molecular damage-associated molecular patterns (DAMPs) triggered by cisplatin to activate the STING pathway, thereby synergistically amplifying the STING-TBK1-IRF3 signaling and efficiently triggering an immune response. (iii) Post-target factors: Combining chemotherapy and immunotherapy to harness the immune system for tumor eradication. In conclusion, this study presents an effective approach to addressing the challenges associated with cisplatin in the clinical treatment of OC.
研究领域:
肿瘤学
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
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
·
肿瘤学
·
生物材料科学
✓ 已验证
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
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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