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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Bolun Xu,Xuan Lu,Yuquan Wang,Haihua Ji,Ying Zhang,Yiqun Wan,Hao Wan
Immunogenic cell death (ICD)-based whole-cell personalized cancer immunotherapies present full tumor antigens but suffer from poor immunogenicity, early clearance, and a glutathione (GSH)-rich immunosuppressive tumor microenvironment (TME). Here, we report a TME-responsive immunotherapeutic platform, DTBEI@CS@MnO 2 , which integrates immunogenicity-enhanced dead tumor cell bodies (DTBEI) with Mn 2 + -potentiated innate immunity. Tumor cells preloaded with indocyanine green (ICG) are sequentially functionalized with a chitosan (CS) interlayer followed by MnO 2 adsorption (CS@MnO 2 ) via electrostatic interactions. Upon near-infrared laser irradiation, ICG-mediated photodynamic/photothermal effect induces potent ICD, generating DTBEI. Within the acidic and GSH-enriched TME, the CS@MnO 2 coating disassembles to release DTBEI and MnO 2 . DTBEI provides endogenous antigens and ICD-associated danger signals, while MnO 2 is reduced by GSH to Mn 2 + . The resulting Mn 2 + amplifies DTBEI- and tumor-derived deoxyribonucleic acid-triggered cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation and downstream immune-stimulatory effects, thereby synergistically promoting dendritic cell maturation, antigen cross-presentation, and tumor-specific T-cell priming. Consequently, DTBEI@CS@MnO 2 elicits durable anti-tumor immunity, effectively inhibiting tumor growth and suppressing recurrence and metastasis, while establishing T-cell memory responses. Importantly, this strategy shows broad applicability in multiple tumor models, including CT26 colon cancer, 4T1 breast cancer, and B16F10 melanoma, while maintaining favorable biocompatibility. Overall, these findings highlight a materials-based approach for personalized cancer immunotherapy.
✓ 已验证
产品关联
DOI
高影响因子
NANOTECHNOLOGY
·
2020
·Vol. 31
·期 41
·415301
·
IF 3.551
Qian Zhao,Guangqiang Liu,Hongwen Zhang,Weiping Cai
A simple and cost-effective route to fabricating gold-coated glass nano-stings' arrays is presented for highly efficient surface enhanced Raman spectroscopy (SERS) chips via reactive ion etching of the glass slide covered with polystyrene (PS) colloidal monolayer and sputtering deposition of gold on it. The as-fabricated SERS chips consist of the nearly-hemispherical particles with submicron-size, which are hexagonally arranged into the ordered arrays. There are many short and long Au-coated glass nano-stings standing vertically on the hemispherical particles, showing high density tips (up to 7.0 × 103 μm−2). The formation of such gold-coated glass hierarchically structured array is attributed to the geometry of PS colloidal monolayer and the nanoscale roughness of glass slide's surface. Further, it has been demonstrated that such gold-coated glass array chip is highly SERS-active and can be utilized to detect trace organophosphorous toxicant with the limit below ppt level and good reproducibility in measurements. The intensity of the Raman peak shows the linear relation, in logarithmic scale, with the organophosphorous concentration from ppt to ppm level, exhibiting the possibility of quantitative detection in a large concentration range. This work has demonstrated the cost-effective method to fabricate the high performance SERS chips for trace detection of toxic molecules.
研究领域:
材料科学
·
分析化学
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Pai Wang,Heshi Liu,Lei Guo,Yixin Tang,Tianwei Lan,Rui Zhou,Huiqing Xu,Lu Wang,Xue Wang,Baiqiao Chen,Yixing Wang,Siyuan Wang,Chang Liu,Jie Chen,Caina Xu,Quan Wang,Huayu Tian
Colorectal cancer (CRC) remains a major global health burden as the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. While combination chemotherapy and immune agonists hold potential to overcome tumor heterogeneity through multi-pathway modulation, their therapeutic efficacy remains limited by off-target drug distribution and immunosuppressive tumor microenvironment (TME). To address this, we developed a tumor-targeted chemo-immunotherapy platform by encapsulating irinotecan (CPT-11) and resiquimod (R848) in hyaluronic acid (HA) coated MIL-100(Fe) metal-organic frameworks (CRMH NPs), enabling CD44-mediated delivery and synergistic anti-tumor responses. The system enabled controlled drug release in the acidic TME, promoting immunogenic cell death (ICD), inducing the cGAS-STING pathway and activating immune cells. In vitro , CRMH NPs induced significant ICD, as evidenced by the release of damage-associated molecular patterns (DAMPs) like high mobility group box 1 (HMGB1) and calreticulin (CRT), and matured dendritic cells (DCs), which triggered by TLR7 agonist, enhancing immune responses. It also activated the cGAS-STING pathway, which could efficiently induce the targeted cells to produce type I interferon (IFN) and proinflammatory cytokines, thereby enhancing T cell activation and recruitment. In vivo , CRMH NPs significantly reduced tumor growth in CT26 mouse models, activated innate immune signaling, and increased immune cell infiltration, demonstrating superior anti-tumor effects compared to free drugs and other nanoparticle formulations. Furthermore, CRMH NPs upregulated PD-L1 expression on tumor cells, suggesting potential synergy with immune checkpoint blockade therapy. Combining CRMH NPs with anti-PD-L1 therapy enhanced anti-tumor immunity, particularly in distant tumors, highlighting a promising approach to overcoming immune evasion and achieving durable tumor regression. These findings supported CRMH NPs as a versatile and effective platform for chemo-immunotherapy in CRC. Statement of Significance Colorectal cancer (CRC) remains a major global health challenge with limited treatment efficacy due to tumor heterogeneity and immunosuppression. This study introduces a novel tumor-targeted nanoparticle platform, CRMH NPs, which co-deliver the chemotherapeutic drug irinotecan (CPT-11) and the immune agonist resiquimod (R848) using hyaluronic acid-coated MIL-100(Fe) metal-organic frameworks. CRMH NPs enhance drug delivery, induce immunogenic cell death, and activate the cGAS-STING pathway, synergizing chemotherapy and immunotherapy. Demonstrating superior tumor suppression and immune activation in preclinical models, this platform overcomes key limitations of current therapies, such as off-target effects and immune evasion. Its combination with anti-PD-L1 therapy further improves outcomes, offering a promising strategy for durable CRC treatment. This work advances nanomedicine and immuno-oncology, providing a transformative approach for cancer therapy.
研究领域:
纳米医学
·
免疫治疗
·
肿瘤学
·
药物递送
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2025
·
IF 3.6
Zeyue Sun,Xiaojun Li,Xueheng Sun,Liuting Chen,Zihang Wang,Xin Feng,Luying Wang,Wenjie Jin,Xin Sun,Jiaju Lu
Bone regeneration is frequently impaired by excessive reactive oxygen species (ROS) and prolonged inflammation, which disrupt the immune microenvironment and hinder osteogenesis. The stimulator of interferon gene (STING) pathway is an innate immune pathway and a critical mediator of the inflammatory response, has been increasingly implicated in inflammatory bone loss and impaired repair. While STING inhibition represents a promising therapeutic strategy, its effective implementation within the bone microenvironment requires spatiotemporally controlled delivery. Here, we developed an injectable and photocrosslinkable hydrogel system (GMPP+H151) that integrates ROS-responsive scavenging with targeted STING inhibition to synergistically guide immune microenvironment remodeling and bone regeneration. The GMPP hydrogel was fabricated through dual crosslinking of phenylboronic acid (PBA)-modified gelatin (GelMA) and polyvinyl alcohol (PVA), endowing it with self-healing properties and ROS-scavenging capacity. H151, a small molecule inhibitor of STING, was caged by PBA chemistry for on-demand release under oxidative stress. The GMPP+H151 can significantly reduce ROS levels in macrophages and promote their phenotypic differentiation from M1 to M2 by suppressing the STING pathway, downregulating pro-inflammatory cytokines, and upregulating anti-inflammatory factors. Furthermore, it efficiently enhanced survival, spreading, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), leading to increased expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). This study presents a smart, multifunctional hydrogel drug delivery system that integrates immunomodulation and osteoinduction, offering a promising strategy for promoting osteogenic differentiation and in situ bone defect repair.
研究领域:
生物材料
·
组织工程
·
免疫调节
·
再生医学
·
干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Qi Long,Yuliang Yang,Fangling Liao,Haoting Chen,Dongyue He,Shengliang Li,Li Pengcheng,Weisheng Guo,Yafang Xiao
Photothermal immunotherapy has shown great potential for efficient cancer treatment. However, the immunosuppressive tumor microenvironment forms a heavy barrier for photothermal-induced anti-tumor immunity by inhibiting dendritic cells (DCs) maturation and cytotoxic T cell response. Moreover, the lack of reliable spatiotemporal imaging modalities makes photothermal immunotherapy difficult to guide tumor ablation and monitor the therapeutic outcomes in real time. Herein, we designed a theranostic thermosensitive liposome (PLDD) as a versatile nanoplatform to boost adaptive anti-tumor immunity of photothermal immunotherapy and achieve multiple bioimaging modalities in a real-time manner. The PLDD contains two major functional components: a multifunctional photothermal agent (DTTB) and an immune potentiator STING pathway agonist (DMXAA). Upon irradiation, the heat generated by DTTB induced the immunogenic cell death (ICD) of the tumor and dissociated the structure of thermosensitive liposome to release DMXAA, which ultimately activated the STING pathway and promoted the ICD-induced immune response by increasing DC cells maturation and T cell recruitment. Meanwhile, the DTTB in PLDD displayed excellent second near-infrared (NIR-II) fluorescence and photoacoustic (PA) dual-modal imaging, which provided omnibearing information on the tumor and guided the subsequent therapeutic operation. Therefore, this versatile PLDD with light-triggered promotion of anti-tumor immunity and multiple spatiotemporal imaging profiles holds great potential for the future development of cancer immunotherapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Haoye Li,Qingwen Yang,Haitong Wu,Jianying Guo,Zhaoxin Tang,Jianzhao Liao
Terbuthylazine (TBA), a triazine herbicide, is extensively employed in agriculture for its wide range of effectiveness. However, prolonged utilization of TBA can pose a potential hazard to animals and human health. Here, a total of 180 broiler chickens ( Gallus gallus ) were stochastically assigned to three groups (control group, 0.4 mg/kg TBA group, and 4 mg/kg TBA group) for investigating the impact of TBA on cardiotoxicity. The results revealed that TBA exposure resulted in pathological alterations in the myocardium . Moreover, TBA exposure activated cGAS-STING pathway and markedly elevated the mRNA and protein expression levels of innate immune response (cGAS, STING, TBK1, and IRF3) in myocardium. Additionally, NF-κB signal was also activated under TBA exposure, which was characterized by the increasing mRNA expression levels of NF-κB, IKKα and the protein expression levels of p-NF-κB/NF-κB, IKKα, p-IκBα/IκBα in the TBA treatment groups. Meanwhile, the expression of pro-inflammatory cytokines (TNF-α and IL-1β) were also significantly increased. In summary, our findings suggested that cGAS-STING/NF-κB pathway functionated in the innate immune response and inflammation in myocardium brought on by TBA exposure, which provided new insights into the TBA toxicology.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2023
·
IF 4.4
Huimin Lv,Peng Chen,Yang Wang,Lianbin Xu,Kai Zhang,Jinshan Zhao,Huawei Liu
ABSTRACT This study aimed to determine the effects of chlorogenic acid ( CGA ) on the growth performance, intestinal health, immune response, and mitochondrial DNA ( mtDNA )–cyclic GMP–AMP synthase ( cGAS )–stimulator of interferon genes ( STING ) signaling pathway in broilers under necrotic enteritis ( NE ) challenge. The 180 one-day-old male Cobb 500 broilers with similar body weight of 44.59 ± 1.39 g were randomly allocated into three groups. The groups were control diet (Control group), control diet + NE challenge (NE group), and control diet + 500 mg/kg CGA + NE challenge (NE + CGA group), with six replicates per treatment. All broilers except the Control group were given sporulated coccidian oocysts (day 14) and Clostridium perfringens (days 19-21) by oral gavage. Our findings showed that CGA improved the growth performance and intestinal morphology in broilers under NE challenge. CGA supplementation elevated the barrier function in broilers under NE challenge, which reflected in the decreased serum concentrations of D-lactate and diamine oxidase, and upregulated jejunal protein expression of occludin. CGA supplementation also improved the immune function, which reflected in the increased concentrations and gene expressions of anti-inflammatory factors, and decreased concentrations and gene expressions of pro-inflammatory factors. CGA supplementation further enhanced intestinal cell proliferation and differentiation, which manifested in the increased number of goblet cells and positive cells of proliferating cell nuclear antigen on days 28 and 42. Furthermore, CGA supplementation decreased the mtDNA (day 42) and mitochondrial reactive oxygen species levels (days 28 and 42), and increased the mitochondrial membrane potential (day 42) and mitochondrial complex Ⅰ (days 28 and 42) or Ⅲ (day 28) activity. Broilers challenged with NE had upregulated jejunal protein expressions of cGAS, phospho-TANK-binding kinase 1, and phospho-interferon regulatory factor 7 compared with the Control group, which were downregulated after CGA supplementation. In conclusion, dietary supplementation CGA could protect against intestinal inflammation and injury by reducing the leakage of mtDNA and inactivating the cGAS–STING signaling pathway in broilers under NE challenge.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Jun-Jun Wu,Guan-Jie Chen,Chen-Yuan Fan,Fan Shen,Yi Yang,Wei Pang,Zhen-Nan Zhao,Hong-Xin Guan,Huan Wu,Ying Lu,Ya-Juan Fu,Qi Chen,Yong-Tang Zheng,Songying Ouyang
The pandemics induced by emerging SARS-CoV-2 variants and monkeypox virus infection have triggered the urgent need for broad-spectrum vaccines. Except for “super” antigen designs, pattern recognition receptor (PRR) agonist-based adjuvants might blaze a new trail, through enhancing the immune response of conserved antigen epitopes shared among variants for cross-protection. Ideal adjuvants with proper adjustments could be conveniently applied to different antigens and antigen types in response to new pandemics. However, general strategies for modulating PRR agonist-based adjuvant properties to tailor the optimal immunity remain to be further explored. Here, an adjuvant platform STINGsome is described, composed of a STING agonist and pH-switchable IP9 liposomes, to simulate viral infection via STING activation and necroptosis. STINGsomes function as an efficient adjuvant to elicit broad and potent immune responses against multiple SARS-CoV-2 VOCs (Omicron BA.1, BA.2, BA.3, BA.4/5) and a monkeypox virus. More importantly, the adjuvant properties of STINGsomes can be tuned by simply adjusting the IP9 percentage, owing to distinct kinetics from local release to lymph node stimulation. Thus, this study provides a relatively simple strategy to adapt an adjuvant platform to different pathogenic antigens, ultimately achieving optimal protective responses.
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Tao Jiang,Feikai Zhu,Xintao Gao,Xiaochen Wu,Wenyong Zhu,Chuanlong Guo
Acute kidney injury (AKI) is a common clinical problem with no effective treatment. Excessive folic acid (FA) induced kidney tubular injury is characterized by oxidative stress and inflammation, and is a common model of AKI. The excellent pharmacological activity of naringenin (NAR) makes it a potential agent for treating AKI, but its poor solubility limits its application. This study prepared NAR loaded nanoparticles (FU/PVP-NAR) using fucoidan (FU) and polyvinylpyrrolidone (PVP) as carriers, with a particle size of 23.96 ± 2.77 nm. In vitro studies showed that FU/PVP-NAR inhibited excessive FA induced proliferation inhibition, accumulation of reactive oxygen species (ROS), and disruption of mitochondrial membrane potential (MMP) of HK-2 cells. Further confirmed that FU/PVP-NAR inhibited FA induced DNA damage and Cyclic GMP–AMP synthase (cGAS)-stimulator of interferon genes (STING) activation. In vivo studies showed that excessive FA induced AKI features in mice, such as elevated serum creatinine (SCr) and blood urea nitrogen (BUN) levels, accompanied by pathological damage to kidney tissues. The above AKI characteristics induced by FA were alleviated by FU/PVP-NAR. FU/PVP-NAR also inhibited the decrease in antioxidant enzyme levels in kidney tissues induced by FA. Furthermore, in vivo mechanism studies indicated that FU/PVP-NAR inhibited the release of inflammatory factors by inhibiting DNA damage-cGAS-STING pathway. In summary, this study provided the possibility for FU/PVP-NAR as a potential candidate drug for treating FA induced AKI.
研究领域:
药理学
·
肾脏病学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
·
2025
·
IF 1.8
Jiaojiao Ren,Jun Ying,Haijian Liu,Shanshan Hu,Jiangdong Li,Danfei Zhou
Background: This study was designed to explore the action mechanism of stimulator of interferon genes (STING) on the differentiation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment of lung cancer.Methods: Bioinformatics analysis yielded a potential pathway for STING to regulate MDSC differentiation, the interferon regulatory factor 3 (IRF3)/NF-κB axis. The transfection efficiency of STING overexpression plasmid and small interfering RNA against IRF3 (siIRF3) was examined by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection, A9 cells were co-cultured with extracted bone marrow cells (BMCs). MDSC differentiation, protein expression of the IRF3/NF-κB pathway, and changes in nuclear translocation of NF-κB were analyzed by flow cytometry, Western blot, and immunofluorescence staining experiments. A transplanted tumor mouse model was used for in vivo experiments. After cyclic diadenyl monophosphate (CDA; STING agonist) treatment, changes in MDSC differentiation and protein expression of the IRF3/NF-κB axis in transplanted tumors were verified by immunohistochemical staining, qRT-PCR, and Western blot.Results: Coculture of A9 cells and BMCs promoted MDSC differentiation, inhibited activation of IRF3/NF-κB signal in A9 cells, and boosted nuclear translocation of NF-κB. However, after the upregulation of STING, IRF3/NF-κB signal was activated, while MDSC differentiation and nuclear translocation of NF-κB were inhibited. SiIRF3 reversed the effects of STING overexpression. In vivo, CDA dampened MDSC differentiation and promoted protein expression of the IRF3/NF-κB axis.Conclusion: STING signal in lung cancer cells inhibits MDSC differentiation through activation of the IRF3/NF-κB pathway.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2025
·
IF 7.3
Ziyan Wang,Wei Zhang,Ziyan Liu,Danyang Huang,Huiwen Kang,Jingyu Wang,Guangyu Jiang,Ai Gao
BDE-209 has a causal relationship with adverse health outcomes. However, research on its effect on bone homeostasis is relatively lacking. This study examined the relationship between BDE-209 exposure and bone health, as well as the underlying mechanisms, using both in vitro and in vivo models. In animal studies, female SD rats were administered BDE-209 for 60 days. Bone mineral density, bone microstructure, gut microbiota, and inflammaging markers were measured. Furtherly, THP-1 cell-derived macrophages were treated with a culture medium containing population-relevant dose of BDE-209 or sodium butyrate. The expression of M1 macrophage markers, osteoclast markers, and inflammatory cytokines was measured. Then macrophages were induced by osteoclast conditioned medium to evaluate the effect of BDE-209 on their differentiation into osteoclasts. Results showed reduced humeral bone density, enhanced osteoclast activity, upregulation of IL-1β, TNF-α, IL-6, and activation of PGC-1α/NAD + /cGAS-STING in the exposed group. 16s sequencing revealed that BDE-209 disrupts the abundance of the gut microbiota, notably a reduction in Lachnospiraceae . In vitro, BDE-209 can stimulate macrophages to differentiate more osteoclasts and activate the cGAS-STING pathway, while sodium butyrate can inhibit these effects. This study reveals that gut microbiota dysbiosis is involved in BDE-209-induced bone homeostasis disorder through inflammatory aging and sodium butyrate can mitigate this effect. Overall, this study provides research data for the precaution and treatment of osteoporosis associated with BDE-209 exposure.
研究领域:
毒理学
·
免疫学
·
骨生物学
·
微生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）