BIOMATERIALS
·
2025
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IF 12.9
Yuanlin Wang,Yaqian Han,Jingshi Li,Zhaotong Wang,Kai Li,Tiancheng Bai,Lei Wang,Ye Sun,Chunying Chen,Miao Yu
Ferroptosis serves as a pivotal mechanism in diverse clinical chemotherapeutics and physiological processes, profoundly impacting tumor metabolism and the tumor microenvironment. Recently, the immunosuppression induced by ferroptosis has raised major concerns regarding tumor recurrence upon ferroptosis-based antitumor therapies. However, due to the lack of cell specificity, the antitumor and immunosuppressive effects in ferroptosis are inherently intertwined. Herein, we address the conflicting challenges between immunosuppression and antitumor efficacy in ferroptosis-based therapy by enabling cell-specific ferroptosis, thereby targeting tumors while sparing immune cells. By employing a specially designed nanoagent, i.e. , ferrous selenide half-shell-covered gold, we induce notable upregulation of glutathione peroxidase 4 (GPX4) and downregulation of prostaglandin E2, leading to an increase in CD 4+ and CD 8+ T cell populations and intense antitumor immune responses. Despite the elevated level of GPX4, significant tumor cell ferroptosis is achieved, which is further promoted by the agent's photothermal and photocatalytic effects. Consequently, long-term immunological memory is established, yielding a long-lasting and recurrence-free antitumor efficacy spanning at least 200 days post-treatment. This work unlocks an avenue to balance immunosuppression reversal with tumor inhibition in ferroptosis-based therapies, providing promising prospects for antitumor therapies facing immunological hurdles in the tumor microenvironment.
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
PHYTOCHEMISTRY
·
2020
·
IF 3.044
Ming Zhou,Xiaogang Peng,Jia Zhou,Ye Liu,Xianggao Meng,Hanli Ruan
Six undescribed triterpenoids , schincarins A‒F, categorized as the preschisanartane (schincarin A), 3,4-secocycloartane (schincarins B‒D), 3,4; 9,10-disecocycloartane (schincarin E), and 3,4-secolanostane (schincarin F) classes, along with twelve known analogues, were obtained from the stems and leaves of Schisandra incarnata Stapf. Their structures were elucidated on the basis of extensive spectroscopic analyses. The absolute configuration of schincarin A was corroborated by analysis of the experimental ECD spectrum, and single-crystal X-ray diffraction with Mo K α irradiation. Schincarin A represented the first example of preschisanartane-type triterpenoid with two oxa-bridged hemiketals . Among the selected compounds which were evaluated for immunosuppressive activities, schincarin C and kadsudilactone A showed potential inhibition against ConA-induced T-cell proliferation with IC 50 values of 5.83 and 6.32 μ M, and LPS-induced B cell proliferation with IC 50 values of 10.21 and 11.49 μ M, respectively.
研究领域:
植物化学
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药理学
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有机化学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-20
·
IF 16.6
Zhou Songlei,Huang Yukun,Chen Yu,Liu Yipu,Xie Laozhi,You Yang,Tong Shiqiang,Xu Jianpei,Jiang Gan,Song Qingxiang,Mei Ni,Ma Fenfen,Gao Xiaoling,Chen Hongzhuan,Chen Jun
The limited benefits of immunotherapy against glioblastoma (GBM) is closely related to the paucity of T cells in brain tumor bed. Both systemic and local immunosuppression contribute to the deficiency of tumor-infiltrating T cells. However, the current studies focus heavily on the local immunosuppressive tumor microenvironment but not on the co-existence of systemic immunosuppression. Here, we develop a nanostructure named Nano-reshaper to co-encapsulate lymphopenia alleviating agent cannabidiol and lymphocyte recruiting cytokine LIGHT. The results show that Nano-reshaper increases the number of systemic T cells and improves local T-cell recruitment condition, thus greatly increasing T-cell infiltration. When combined with immune checkpoint inhibitor, this therapeutic modality achieves 83.3% long-term survivors without recurrence in GBM models in male mice. Collectively, this work unveils that simultaneous reprogramming of systemic and local immune function is critical for T-cell based immunotherapy and provides a clinically translatable option for combating brain tumors.
研究领域:
肿瘤学
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免疫学
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纳米技术
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HEPATOLOGY
·
2024
·
IF 12.9
Zhang Sitong,Sun Zhongquan,Chen Zhenhua,Bi Yanli,Wei Shenyu,Mao Zhengwei,Jin Jin,Ding Yuan,Wang Weilin
Background & Aims: Liver ischemia-reperfusion injury (IRI) is a common complication of liver transplantation and hepatectomy, and causes acute liver dysfunction and even organ failure. Myeloid-derived suppressor cells (MDSCs) accumulate and play immunosuppressive function in cancers and inflammation. However, the role of MDSCs in liver IRI has not been defined. Approach & Results: We enrolled recipients receiving orthotopic liver transplantation (OLT) and obtained the pre-OLT/post-OLT blood and liver samples. The proportions of MDSCs were significantly elevated after OLT and negatively associated with liver damage. In single-cell RNA-sequencing analysis of liver samples during OLT, two cell clusters with MDSC-like phenotypes were identified and showed maturation and infiltration in post-OLT livers. In mice model, liver IRI mobilized MDSCs and promoted their infiltration in damaged liver, and intrahepatic MDSCs possessed with enhanced immunosuppressive function by up-regulation of STAT3 signaling. Under treatment with αGr-1 antibody or adoptive transfer MDSCs to change the proportion of MDSCs in vivo , we found that intrahepatic MDSCs alleviated liver IRI-induced inflammation and damage by inhibiting M1 macrophage polarization. Mechanistically, bulk RNA-sequencing analysis and in vivo experiments verified that CXCL17 was upregulated by YAP/TEAD1 signaling and subsequently recruited MDSCs via binding with GPR35 during liver IRI. Moreover, hepatic endothelial cells were the major cells responsible for CXCL17 expression in injured livers, among which hypoxia-reoxygenation stimulation activated YAP/TEAD1 complex to promote CXCL17 transcription. Conclusions: Endothelial YAP/TEAD1-CXCL17 signaling recruited MDSCs to attenuate liver IRI, providing evidence of a therapeutic potential for managing IRI in liver surgery. Export
研究领域:
医学
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免疫学
·
肝脏病学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-19
·
IF 15.7
Li Wenchao,Chen SaiSai,Lu Jian,Mao Weipu,Zheng Shiya,Zhang Minhao,Wu Tiange,Chen Yurui,Lu Kai,Chu Chunyan,Shu Chuanjun,Hou Yue,Yang Xue,Shi Naipeng,Chen Zhijun,Zhang Lihua,Zhang Lei,Na Rong,Chen Ming,Ju Shenghong,Zhang Dingxiao,Ma Yi,Xu Bin
Immune checkpoint therapy for prostate cancer (PCa), a classic ‘immune-cold’ tumor characterized by an immunosuppressive tumor microenvironment, failed previously in clinical trials, but the underlying causes remain elusive. Here we find that YY1 + , immunosuppressive macrophages aggregate in the hypoxic areas of PCa. Mechanistically, hypoxia promotes the phase separation of YY1 in the nucleus, where YY1 binds to NUSAP1 and promotes the SUMOylation, phase separation and stabilization of HIF-1α. Either myeloid-specific conditional knockout of YY1 or a treatment with tenapanor for decreasing the YY1–NUSAP1–HIF-1α interaction impairs subcutaneous PCa tumor formation in mouse prostate tumor models. Lastly, a first-generation tetrahedral DNA nanostructure based on the proteolysis targeting chimera technique, termed YY1-DcTAC, allows targeting and degrading YY1 in tumor-associated macrophages for inducing antitumor effects and CD8 + T cell tumor infiltration in mouse tumor models. In summary, our findings underscore the pivotal role of YY1 in the hypoxia/HIF-1α pathway in tumor-associated macrophages and support the targeting of YY1 for treating PCa.
研究领域:
肿瘤生物学
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免疫学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE CHEMICAL LETTERS
·
2022
·
IF 8.455
Hao Gu,Guoxin Dai,Siyu Liu,Yanbing Zhai,Qian Xu,Hongqiang Wu,Wei Xu
Liquid chromatography tandem mass spectrometry (LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices, instrument footprint, operation and maintenance complexity also hinder its expansion as the analytical technique of choice. In this study, a compact LC-MS instrument was developed, in which an assembled liquid chromatograph was coupled with a miniature ion trap mass spectrometer. The overall instrument has a footprint of 69 cm × 31 cm × 31 cm, and it requires no gas supply as well as minimum maintenance. Furthermore, the use of LC-MS is in accord with conventional clinical diagnostic protocols, and the choice of ion trap offers tandem MS performance. The results showed that the use of LC could improve both mixture analysis capability and detection sensitivity of the miniature mass spectrometer. After optimization, feasibility of this instrument in clinical practice was demonstrated by the quantitation of four widely used immunosuppressants in blood samples. Relatively good linearities were obtained, which spanned the reference ranges of effective therapeutic concentrations of each immunosuppressant. Intra-day and inter-day accuracy and precision of analytical method were also assessed. This work showed that a compact LC-MS instrument could be used in clinical diagnosis, either to replace conventional lab-scale instruments or to be used in POCT applications.
研究领域:
分析化学
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医学
✓ 已验证
产品关联
DOI
高影响因子
Nature Nanotechnology
·
2025
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IF 34.9
Zhao Kai,Yan Yu,Jin Xiao-Kang,Pan Ting,Zhang Shi-Man,Yang Chi-Hui,Rao Zhi-Yong,Zhang Xian-Zheng
Chemoresistance and immunosuppression are common obstacles to the efficacy of chemo-immunotherapy in colorectal cancer (CRC) and are regulated by mitochondrial chaperone proteins. Here we show that the disruption of the tumour necrosis factor receptor-associated protein 1 ( TRAP1 ) gene, which encodes a mitochondrial chaperone in tumour cells, causes the translocation of cyclophilin D in tumour cells. This process results in the continuous opening of the mitochondrial permeability transition pore, which enhances chemotherapy-induced cell necrosis and promotes immune responses. On the basis of this discovery we developed an oral CRISPR–Cas9 delivery system based on zwitterionic and polysaccharide polymer-coated nanocomplexes that disrupts the TRAP1 gene in CRC. This system penetrates the intestinal mucus layer and undergoes epithelial transcytosis, accumulating in CRC tissues. It enhances chemotherapeutic efficacy by overcoming chemoresistance and activating the tumour immune microenvironment in orthotopic, chemoresistant and spontaneous CRC models, with remarkable synergistic antitumour effects. This oral CRISPR–Cas9 delivery system represents a promising therapeutic strategy for the clinical management of CRC.
研究领域:
肿瘤学
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分子生物学
·
基因编辑
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Jinlian Liu,Ke Song,Bingqi Lin,Zhenfeng Chen,Zirui Zuo,Yixing Fang,Qi He,Xiaodan Yao,Zhifeng Liu,Qiaobing Huang,Xiaohua Guo
Neutrophils and T lymphocytes are closely related to occurrence of immunosuppression in sepsis. Studies have shown that neutrophil apoptosis decreases and T lymphocyte apoptosis increases in sepsis immunosuppression, but the specific mechanism involved remains unclear. In the present study, we found Toll-like Receptor 2 (TLR2) and programmed death-ligand 1 (PD-L1) were significantly activated in bone marrow neutrophils of wild-type mice after LPS treatment and that they were attenuated by treatment with C29, an inhibitor of TLR2. PD-L1 activation inhibits neutrophil apoptosis, whereas programmed death protein 1 (PD-1) activation promotes apoptosis of T lymphocytes, which leads to immunosuppression. Mechanistically, when sepsis occurs, pro-inflammatory factors and High mobility group box-1 protein (HMGB1) passively released from dead cells cause the up-regulation of PD-L1 through TLR2 on neutrophils. The binding of PD-L1 and PD-1 on T lymphocytes leads to increased apoptosis of T lymphocytes and immune dysfunction, eventually resulting in the occurrence of sepsis immunosuppression. In vivo experiments showed that the HMGB1 inhibitor glycyrrhizic acid (GA) and the TLR2 inhibitor C29 could inhibit the HMGB1/TLR2/PD-L1 pathway, and improving sepsis-induced lung injury. In summary, this study shows that HMGB1 regulates PD-L1 and PD-1 signaling pathways through TLR2, which leads to immunosuppression.
研究领域:
免疫学
·
传染病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Yinan Wang,Wenjuan Zhang,Aijing Li,Maoyong Song
Tetrachlorobisphenol A (TCBPA) is used as flame retardant, and it has been widely detected in the environmental and human samples. TCBPA is an endocrine disrupting chemical, but its effects on the immune system remains poorly understood. Here the effects of TCBPA on immune system were studied using combined in vivo and in vitro assays. Results showed that TCBPA could suppress the immune response in BALB/c mice via reducing the ratio of CD3 + T lymphocytes to regulatory T cells. Moreover, TCBPA exposure significantly induced the increasing secretion of four pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α) and four anti-inflammatory cytokines (IL-4, IL-5, IL-10, GM-CSF) in mice serum. Interestingly, uterine edema was observed in over 80% TCBPA-treated mice after 14- day exposure. TCBPA was detected in 18.6% serum samples of 150 female volunteers in this study. Therefore, our findings provided evidence that TCBPA exposure may cause adverse outcomes on immune system and uterus, suggesting that environmental exposure of TCBPA, as well as its adverse effects on human health should be of concern.
研究领域:
免疫学
·
环境科学
·
生殖健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2018
·
IF 2.441
Yao Li,Sheng Guo,Tingting Hua,Yanyan Wang,Dandan Wei,Ming Zhao,Shulan Su,Jin-ao Duan
The fruit of Ziziphus jujuba ( Jujubae Fructus ) has been used as food and crude drug for thousands of years. Although several chemical and biological studies have revealed triterpenic acid as the main bioactive constituent of Jujubae Fructus responsible for immune-regulatory activity, only few pharmacokinetic studies have been conducted. To comprehend the kinetics of triterpenic acids and promote their curative application, a sensitive and efficient ultra-performance liquid chromatography coupled with mass spectrometry method (UPLC-MS/MS) was established. UPLC-MS/MS was applied for the simultaneous determination of ceanothic acid, epiceanothic acid, pomonic acid, alphitolic acid, maslinic acid , betulinic acid , and betulonic acid in normal and immunosuppressed rat plasma samples. After sample preparation, chromatographic separation was performed on an Acquity UPLC BEH C 18 column (2.1 × 100 mm, 1.7 μm) with acetonitrile : methanol (1:1, v/v) and 0.5% ammonium acetate in water as mobile phase . The established method was validated and found to be specific, accurate, and precise for the seven triterpenic acids, and was successfully applied for the pharmacokinetic study of rat plasma samples. The results showed that the pharmacokinetic parameters (C max , T max , AUC 0–t , AUC 0–∞, and CLz/F) in the plasma samples of immunosuppressed rats were significantly different from those in normal rats, and might provide an insight for the clinical usage of triterpenic acids from Jujubae Fructus .
研究领域:
药理学
·
分析化学
·
中药学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Duo Wang,Tianqi Nie,Yifei Fang,Linzhu Zhang,Chao Yu,Ming Yang,Ruijie Du,Junjie Liu,Lei Zhang,Liangzhu Feng,Haidong Zhu
Radiofrequency ablation (RFA), a thermoablative treatment for small hepatocellular carcinoma (HCC), has limited therapeutic benefit for advanced HCC patients with large, multiple, and/or irregular tumors owing to incomplete RFA (iRFA) of the tumor mass. It is first identified that iRFA-treated tumors exhibited increased pyruvate kinase M2 (PKM2) expression, exacerbated tumor immunosuppression featured with increased tumor infiltration of suppressive immune cells and increased proliferation, and programmed cell death ligand 1 expression of cancer cell and ultimately a poor prognosis. Herein, a multifunctional nanomedicine is fabricated by encapsulating nanoassemblies of anti-PD-L1 and spermidine-grafted oxidized dextran with shikonin-containing lipid bilayers to reverse iRFA-induced treatment failure. Shikonin, a PKM2 inhibitor, is used to suppress glycolysis in cancer cells, while anti-PD-L1 and spermidine are introduced to collectively reprogram the proliferation and functions of infiltrated CD8+ T lymphocytes. Combined with iRFA, which promoted the exposure of tumor antigens, the intravenous injection of liposomal SPS-NPs effectively stimulated dendritic cell maturation and reversed tumor immunosuppression, thus eliciting potent antitumor immunity to synergistically suppress the growth of residual tumor masses and lung metastasis. The as-prepared liposomal nanomedicine is promising for potentiating the therapeutic benefits of RFA toward advanced HCC patients through reprogramming iRFA-induced tumor immunosuppression.
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
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-19
·
IF 12.6
Song Zhengwei,Sun Quanwei,Yang Wenshuo,Li Yunlong,Hu Chaoyu,Chen Chen,Liu Kang,Shen Wei,Yang Ye,Yin Dengke
Background Prolonging the duration of photodynamic therapy (PDT) enhances the level of reactive oxygen species (ROS), thereby facilitating tumor ablation. However, our findings indicated that excessive ROS not only induces epithelial-mesenchymal transition (EMT) but also creates an immunosuppressive microenvironment in tumor, thereby triggering tumor metastasis. Methods We initially developed neutrophil membrane hybrid liposomes (NLs) that can specifically target inflamed tumor tissues following PDT. Then, we utilized NLs to encapsulate the antioxidant nanozyme FeGA and the antiplatelet drug Lysine Acetylsalicylate (LAS), resulting in the formulation NLASF. Results Experimental results demonstrated that FeGA effectively scavenges ROS, thereby reversing the immunosuppressive microenvironment induced by prolonged PDT. Furthermore, the incorporation of LAS effectively disrupts the interaction between tumor cells and platelets, mitigating tumor EMT and inhibiting hematogenous tumor metastasis. In a breast cancer mouse model, we observed that treatment with NLASF led to a near-complete suppression of tumor lung metastasis following the prolonged PDT. Additionally, the in vivo application of NLASF did not result in any blood toxicity or organ toxicity, highlighting its significant advantages over the free drugs group. Conclusions This study provides a novel approach to enhance the efficacy of PDT and successfully suppress PDT-mediated tumor metastasis.
研究领域:
肿瘤学
·
免疫学
·
药剂学
✓ 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）