Theranostics
·
2020
·
IF 8.579
Weijie Ma,Daoming Zhu,Jinghua Li,Xi Chen,Wei Xie,Xiang Jiang,Long Wu,Ganggang Wang,Yusha Xiao,Zhisu Liu,Fubing Wang,Andrew Li,Dan Shao,Wenfei Dong,Wei Liu,Yufeng Yuan
Rationale : Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world. Apart from traditional surgical resection, radiotherapy, and chemotherapy, more recent techniques such as nano-photothermal therapy and biotherapy are gradually being adopted for the treatment of HCC. This project intends to combine the advantages of nanoscale drug delivery systems with the targeting ability of CAR-T cells. Method : Based on cell membrane-coated nanoparticles and cell membrane-targeting modifications, a novel nanomaterial was prepared by coating CAR-T cell membranes specifically recognizing GPC3 + HCC cells onto mesoporous silica containing IR780 nanoparticles. Subsequently, the physical properties were characterized, and the in vitro and in vivo targeting abilities of this nanoparticle were verified. Results : CAR-T cells were constructed which could recognize GPC3 expressed on the cell surface of HCC cells. Then the isolated CAR-T cell membrane was successfully coated on the IR780 loaded mesoporous silica materials, as verified by transmission electron microscopy. The superior targeting ability of CAR-T cell membrane coated nanoparticles compared to IR780 loaded mesoporous silica nanoparticles was verified, both in vitro and in vivo . Conclusion : This new nanomaterial exhibits photothermal antitumor abilities along with enhanced targeting abilities, suggesting a promising strategy for the treatment of HCC.
研究领域:
肿瘤学
·
纳米技术
·
生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2022
·
IF 6.633
Shan Lu,Xuelin Dong,Binbin Zhang,Qi Zhou,Xinwei Zhang,Yonggui Liao,Yajiang Yang,Hong Wang
In this work, a dual-channel probe based on a complex of Eriochrome Black T (EBT) and Eu 3+ ions (denoted as EBT/Eu 3+ ) was used to sense four kinds of tetracyclines (TCs). UV–Vis and fluorescence spectra indicated that EBT/Eu 3+ molecule has the ability to emit dual channel signals of color and fluorescence. When TCs with different structures were added to the EBT/Eu 3+ solution, the color and the fluorescence intensities of EBT/Eu 3+ solution varied with TCs structure. FT-IR spectra revealed that a coordinating reaction occurred between acylamino groups, hydroxyl groups of A-ring in TCs and Eu 3+ ions. The coordinating ratio was 1: 2. Utilizing dual channel signals as well as the aid of principal component analysis (PCA), EBT/Eu 3+ was capable of discriminating not only single TCs with concentrations in nano-molar level, but also binary mixtures of TCs. The results of controlled experiments on various interfering substances and other antibiotics proved that this method has high selectivity for TCs detection. Furthermore, this two-channel sensor array based on EBT/Eu 3+ can also be used for the discrimination of unknown TCs in commercially available pork and honey with the 100% recognition accuracy. These results indicated that TCs with different structures can be rapidly discriminated by using a single and easily prepared sensor array.
研究领域:
分析化学
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传感器
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环境科学
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食品安全
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DOI
高影响因子
CANCER LETTERS
·
2021
·
IF 8.679
Ya-Nan Tan,Yong-Peng Li,Jian-Dong Huang,Min Luo,Shan-Shan Li,Anne Wing-Mui Lee,Fu-Qiang Hu,Xin-Yuan Guan
The response rate of anti-PD therapy in most cancer patients remains low. Therapeutic drug and tumor-infiltrating lymphocytes (TILs) are usually obstructed by the stromal region within tumor microenvironment (TME) rather than distributed around tumor cells, thus unable to induce the immune response of cytotoxic T cells. Here, we constructed the cationic thermosensitive lipid nanoparticles IR780/DPPC/BMS by introducing cationic NIR photosensitizer IR-780 iodide (IR780) modified lipid components, thermosensitive lipid DPPC and PD-1/PD-L1 inhibitor BMS202 (BMS). Upon laser irradiation, IR780/DPPC/BMS penetrated into deep tumor, and reduced cancer-associated fibroblasts (CAFs) around tumor cells to remodel the spatial distribution of TILs in TME. Interestingly, the cationic IR780/DPPC/BMS could capture released tumor-associated antigens (TAAs), thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. Moreover, IR780/DPPC/BMS initiated gel-liquid crystal phase transition under laser irradiation, accelerating the disintegration of lipid bilayer structure and leading to the responsive release of BMS, which would reverse the tumor immunosuppression state by blocking PD-1/PD-L1 pathway for a long term. This combination treatment can synergistically exert the antitumor immune response and inhibit the tumor growth and metastasis.
研究领域:
肿瘤学
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免疫疗法
·
纳米医学
·
癌症研究
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Xin-Yu Shen,Jing-Mei Lu,Yu-Nan Lu,Guang-Nan Jin,Jing-Wen Ma,Jing-He Wang,Yu Wang,Xiang Xu,Lian-Xun Piao
Toxoplasma gondii ( T. gondii ) is an obligate intracellular protozoan parasite that causes pulmonary toxoplasmosis, although its pathogenesis is incompletely understood. There is no cure for toxoplasmosis. Coixol, a plant polyphenol extracted from coix seeds, has a variety of biological activities. However, the effects of coixol on T. gondii infection have not been clarified. In this study, we infected a mouse macrophage cell line (RAW 264.7) and BALB/c mice with the T. gondii RH strain to establish infection models in vitro and in vivo , respectively, to explore protective effects and potential mechanisms of coixol on lung injury caused by T. gondii infection. Anti- T. gondii effects and underlying anti-inflammatory mechanisms of coixol were investigated by real-time quantitative PCR, molecular docking, localized surface plasmon resonance, co-immunoprecipitation, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence microscopy. The results show that coixol inhibits T. gondii loads and T. gondii -derived heat shock protein 70 ( T.g. HSP70) expression. Moreover, coixol reduced inflammatory cell recruitment and infiltration, and ameliorated pathological lung injury induced by T. gondii infection. Coixol can directly bind T.g. HSP70 or Toll-like receptor 4 (TLR4) to disrupt their interaction. Coixol prevented overexpression of inducible nitric oxide synthase, tumor necrosis factor-α, and high mobility group box 1 by inhibiting activation of the TLR4/nuclear factor (NF)-κB signaling pathway, consistent with effects of the TLR4 inhibitor CLI-095. These results indicate that coixol improves T. gondii infection-induced lung injury by interfering with T.g. HSP70-mediated TLR4/NF-κB signaling. Altogether, these findings suggest that coixol is a promising effective lead compound for the treatment of toxoplasmosis.
研究领域:
寄生虫学
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免疫学
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药理学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2022
·Vol. 13
·期 4
·1-12
·
IF 9.685
Liu Qihui,Yang Quanli,Wu Zengfeng,Chen Yanfang,Xu Miaomiao,Zhang Hua,Zhao Jiliang,Liu Zonghua,Guan Zerong,Luo Jing,Li Zhi-yong,Sun Guodong,Wen Qiong,Xu Yan,Li Zhenhua,Chen Kebing,Ben Xiaosong,He Wanchun,Li Xueshi,Yin Zhinan,Hao Jianlei,Lu Ligong
Liver fibrosis represents a severe stage of liver damage, with hallmarks of inflammation, hepatic stellate cell activation, and extracellular matrix accumulation. Although previous studies demonstrated γδ T cells are involved in liver fibrosis, the precise role and mechanisms of γδ T cells migrating to fibrotic liver have not been elucidated. Here, we aim to investigate the functional subsets of γδ T cells in hepatic fibrosis and to further explore the underlying causes and drivers of migration. In this study, we observed that γδ T cells accumulate in fibrotic liver. Adoptive transfer of γδ T, especially Vγ4 γδ T subset, can significantly alleviate liver fibrosis. In addition, CCl 4 treatment also leads to activation of mTOR signaling in γδ T cells. Genetic deletion of the Rictor gene, but not Raptor, in γδ T cells markedly exacerbated liver fibrosis. Mechanistically, CCl 4 -induced liver injury causes macrophage accumulation in the liver, and IL-1β produced by macrophages promotes mTORC2 signaling activation in γδ T cells, which upregulates T-bet expression and eventually promotes CXCR3 transcription to drive γδ T cell migration. Moreover, hepatic γδ T cells ameliorated liver fibrosis by cytotoxicity against activated hepatic stellate cells in FasL-dependent manner, and secrete IFN-γ to inhibit the differentiation of pro-fibrotic Th17 cells. Thus, IL-1β-activated mTORC2 signaling in γδ T cells upregulates CXCR3 expression, which is critical for IFN-γ + γδ T cells migration into the liver and amelioration of liver fibrosis. Our findings indicate that targeting the mTORC2 or CXCR3 in γδ T cells could be considered as a promising approach for γδ T cell immunotherapy against liver fibrosis.
研究领域:
免疫学
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肝病学
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细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
·
2026
·
IF 2.2
Wuwei Xu,Yanxin Xu,Chunyan Yao,Xianmei Fu,Xiaoling Liu,Jinping Fan,Kexue Wang,Yumeng Zhou,Yuefei Li,Ting Hu,Yan Sai,Peng Luo,Tongjian Cai
T-2 toxin is a widely distributed environmental mycotoxin that poses severe neurotoxic risks to humans and animals. Neuroinflammatory responses constitute a key mechanism underlying the neurotoxicity of T-2 toxin. However, its molecular mechanisms for inducing inflammatory responses in the nervous system remain incompletely understood. This study investigated the role of B-cell translocation gene 2 (BTG2) in T-2 toxin-induced microglial activation and evaluated the neuroprotective potential of resveratrol (Res). In vivo experiments demonstrated that exposure to T-2 toxin resulted in spatial learning, memory impairments and locomotor deficits in mice. These behavioral phenotypes were accompanied by neuroinflammation in the hippocampus and cerebral cortex, characterized by microglial activation and the upregulation of BTG2. Res pre-treatment effectively reversed these neurobehavioral deficits and suppressed the neuroinflammatory response. Mechanistic analyses revealed that Res considerably alleviated T-2 toxin-induced TLR4/MyD88/NF-κB pathway activation. In vitro studies using BV-2 microglial cells confirmed these findings. Notably, siRNA-mediated knockdown of BTG2 also abolished TLR4 pathway activation and subsequent cytokine expression induced by T-2 toxin, establishing BTG2 as a critical upstream regulator. Furthermore, RNA sequencing systematically verified that BTG2 regulates the immune response network, specifically targeting the TLR4 cascades. Collectively, these findings provide novel evidence that Res may target the BTG2-regulated TLR4/MyD88/NF-κB signal pathway to exert neuroprotection, providing a promising intervention option for reducing the environmental and health hazards associated with exposure to T-2 toxin
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产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2026
·
IF 6
Yuxi Xiang,Junyu Tan,Xicheng Yan,Yunyun Wu,Chang Yu,Daqing Xia,Jing Zhu,Hongrui Zhu,Jixi Zhang
Abnormal tumor vasculature impedes T-cell migration and compromises immunotherapy. Conventional anti-angiogenic strategies fail to restore the endothelial barrier and adhesion molecules. This limitation hinders long-term therapeutic benefits. Therefore, simultaneously restoring vascular function and activating immunity is essential. Herein, a pH-responsive, salvianic acid A-loaded manganese-aluminum layered double hydroxide nanosystem (S-LDH) was developed for synergistic regulation. In the acidic tumor microenvironment, S-LDH degrades in situ to release salvianic acid A and manganese ions. Released salvianic acid A directly repairs endothelial junctions via the β-catenin/claudin-5 pathway, restoring vascular integrity to promote immune cell infiltration. Concurrently, released manganese ions induce oxidative stress and trigger ICD via Fenton-like reactions while amplifying the cGAS-STING pathway to promote dendritic cell maturation and cytotoxic T-cell responses. Furthermore, STING activation upregulates endothelial adhesion molecules, further facilitating T-cell infiltration. In a 4T1 murine breast cancer model, S-LDH increased CD8+ T-cell infiltration by 10.9-fold and CD4+ T-cell infiltration by 4.3-fold compared with free salvianic acid A, confirming that simultaneous vascular repair and immune activation overcome the endothelial barrier. This work establishes a strategy that repairs tumor endothelial integrity and upregulates adhesion molecules to overcome this limitation by enabling T-cell infiltration.
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Shihui Wang,Qing Xu,Xueqian Peng,Xinman Li,Tianqing Zheng
Conventional CD3-targeting bispecific T cell engagers (BiTEs) have shown limited efficacy in solid tumors, largely due to the highly immunosuppressive tumor microenvironment (TME) and systemic T cell activation-associated toxicity. To address this challenge, we developed a peptide–MHC class I-based T cell engager platform that selectively redirects a specific subset of CD8 + T cells to tumor cells. Using the model ovalbumin (OVA) system, we engineered fusion proteins comprising an OVA peptide–H-2Kᵇ complex linked to an anti-HER2 nanobody (OVA-αHER2), enabling simultaneous engagement of OVA-specific T cells and HER2-expressing tumor cells and inducing potent tumor cell killing in vitro . To overcome the immunosuppressive TME, we further combined a HER2-targeted IL-12 fusion protein with OVA-αHER2, achieving synergistic anti-tumor responses in a mouse B16-HER2 solid tumor model. This treatment enhanced both systemic and intratumoral OVA-specific CD8 + T cell responses, accompanied by increased IFN-γ production in the TME. Together, these findings establish a modular immunotherapy strategy that integrates recruitment of a specific CD8 + T cell subset with localized cytokine-mediated immune reprogramming, providing a potential approach for HER2-positive solid tumors.
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2026
·Vol. 193
·期 8
·583
·
IF 5.4
Naveed Shahzad,Tang Hongyu,Zhao Zhijie,Dai Chuanzhi,Yan Peng,Du Jianqiang,Wu Yayan
Conventional nanoparticle-based colorimetric sensor arrays typically require the synthesis of multiple differently modified nanoprobes as sensing elements, where the process is often complex and the number of available probes is limited. We designed a simple sensor array for bacteria identification using five different metal ions (Al³⁺, Fe³⁺, Cu²⁺, Ni²⁺, Co²⁺) and only one type of T-AgNPs as sensing elements. The bacteria were first treated with metal ions, which altered their surface properties, leading to differential binding with T-AgNPs. Subsequent addition of Cl − induced the etching of T-AgNPs, producing unique color change patterns for bacteria. Combined with multivariate analysis, the array showed clear discrimination of 11 bacterial species, bacterial mixtures, and bacteria at different concentrations in artificial plasma and urine. Linear discriminant analysis (LDA) with leave-one-out cross-validation showed complete separation within the current datasets, although further validation using larger independent datasets and blinded unknown samples is needed. This simple and cost-effective strategy provides a facile and expandable platform for bacterial identification. Graphical abstract
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2020
·
IF 2.369
Hongxia Li,Lijiang Guo
The solubility and phase diagram of the CsCl–MgCl2–H2O ternary system, at a relatively wide temperature range, are significantly important for the extraction of the cesium resources from salt lakes. The isothermal dissolve equilibrium (IDE) method was used to determine the solubility of this ternary system at T = 273.15, 308.15, and 348.15 K, which have not been reported yet. The measured results indicated that the equilibrium solid phases in this ternary system from T = 273.15 to 348.15 K are CsCl, double salt CsCl·MgCl2·6H2O, and MgCl2·6H2O, and correspondingly there are three crystal regions and two cosaturated points for these solid phases. The solubility of the salt increased with the increase of the temperature, and the double salt CsCl·MgCl2·6H2O and CsCl crystal regions also became larger with the increasing temperature. However, the crystal regions of the MgCl2·6H2O solid phase are not enlarged obviously. Based on the solubility and phase diagram of CsCl–MgCl2–H2O at different temperatures, the separation process of CsCl resources has been proposed.
研究领域:
化学
·
材料科学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 2
·607
·
IF 4.9
Jiaxuan Zhao,Youyong Wang,Yixuan Wang,Ge Dong,Han Wu,Yeting Cui,Lixing Gu,Fenfang Zhao,Guanlin Zhao,Jinyu Kang,Qian Zhang,Nan Liu,Ning Wang,Xiao Sun,Yao Xu,Tongcun Zhang,Jiangzhou Shi
The manufacturing process contributes significantly to the proliferation, metabolic state, and functional persistence of chimeric antigen receptor (CAR)-T cells. However, how different culture systems regulate CAR-T cell metabolism and thereby influence their long-term antitumor activity remains poorly understood. In this study, we compared dynamic cultivation using a wave bioreactor with static expansion systems (gas-permeable and conventional T-flasks) for the production of CD99-specific CAR-T cells. CAR-T cells expanded by the wave bioreactor exhibited faster proliferation and stronger cytotoxicity during culture. Upon repeated antigen stimulation, they retained these enhanced functional properties and showed the reduced expression of immune checkpoint molecules, preferentially preserved memory-like subsets, and displayed transcriptional features consistent with memory maintenance and exhaustion resistance. Targeted metabolomic profiling revealed enhanced Tricarboxylic Acid (TCA) cycle activity and features consistent with sustained oxidative phosphorylation, supporting mitochondrial-centered metabolic reprogramming. In a Ewing sarcoma xenograft model, wave bioreactor-cultured CAR-T cells showed a greater percentage of memory-like tumor-infiltrating lymphocytes. Collectively, these results indicate that wave bioreactor-based dynamic cultivation promotes mitochondrial metabolic reprogramming, which is characterized by an enhanced TCA cycle and sustained oxidative phosphorylation, thereby sustaining CAR-T cell functionality and providing a robust platform for the manufacturing of potent and durable cellular therapeutics.
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产品关联
DOI
PubMed
高影响因子
Cancer Immunology Research
·
2025
·
IF 8.2
Liu Chuwei,Liang Heng,Wang Peipei,Xiao Min,Zheng Yuyan,Yan Shijia,Deng Yuan,Liu Ruonian,Wan Arabella H.,Wang Zhi,Lu Xiongbin,Song Wu,He Weiling,Wan Guohui
Immune checkpoint blockade (ICB) has transformed colorectal cancers (CRCs) therapy, yet the majority of microsatellite-stable (MSS) CRCs remain refractory due to insufficient tumor-immune cell crosstalk. Identifying molecular regulators that modulate the tumor immune microenvironment (TIME) is crucial for expanding ICB efficacy. Here, we identified HNRNPA2B1, an RNA-binding protein prominently upregulated in CRC, as a key driver of immune evasion. Despite low cytotoxicity to normal cells, HNRNPA2B1 rewired the TIME by suppressing Cxcl9/Cxcl10-Cxcr3 signaling, CD8+ T-cell infiltration, and MHC class I antigen presentation, resulting in a non-inflamed (“cold”) tumor state. HNRNPA2B1 deletion reprogramed the TIME, enhanced CD8+ T cell-mediated tumor clearance, and sensitized MSS CRCs to ICB. A computational A2B1 score was developed to quantify HNRNPA2B1’simpact on tumor-immune interactions, and showed that it strongly correlated with immune infiltration, epithelial-mesenchymal transition status, and patient prognosis, supporting its potential role as a biomarker for ICB responsiveness in CRC.
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DOI
PubMed
高影响因子
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