FOOD CHEMISTRY
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2019
·
IF 5.399
Gaigai Li,Xufeng Meng,Junmin Wang,Qianqian Wang,Junhong Zhou,Chun Wang,Qiuhua Wu,Zhi Wang
In this study, a porous organic polymer (denoted as Car-DMB) was fabricated by a simple one-step crosslinking polymerization of carbazole and p -dimethoxybenzene for the first time. Then the Car-DMB was served as adsorbent of solid phase extraction to enrich triazine herbicides from white gourd, tomato and soybean milk samples prior to their determination by high performance liquid chromatography. Under the optimal conditions, the response linearity was in the range of 0.3–100.0 ng g −1 for white gourds and tomato samples, and 0.5–100.0 ng mL −1 for soybean milk, with the coefficient of determination higher than 0.996. The detection limits were 0.1–0.2 ng g −1 for white gourd and tomato samples, and 0.15–0.3 ng mL −1 for soybean milk. The adsorption mechanism of the Car-DMB for the triazines was attributed to the strong H-bonding and weak π-π interactions. The efficient extraction for several other compounds demonstrated that Car-DMB holds great potential for diverse analysis applications.
研究领域:
分析化学
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环境科学
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 15
Jinfan Zhou,Gaohua Li,Yunze Xu,Wenhui Ma,Xuehua Zhang,Haitao Yuan,Zilin Tan,Zhenghao Li,Hongwei Yu,Zhenzhao Xu,Zhiqiang Yu,Jiafei Xi,Chaoping Fu,Yanan Wang
The treatment of solid tumors with chimeric antigen receptor natural killer (CAR-NK) cell therapy confronts significant barriers, notably poor cellular infiltration and a highly immunosuppressive tumor microenvironment (TME). To overcome these challenges, we developed selenium-containing polymer nanoparticles (ManNAl-SeNPs) loaded with dibenzocyclooctyne (DBCO)-modified mannose. Metabolic glycoengineering metabolic glycoengineering (MGE) enabled efficient labeling of exogenous DBCO on azide (N 3 ) groups on CAR-NK cells, establishing a bioorthogonal click chemistry targeting strategy, significantly improving the anti-tumor activity of azide-CAR-NK (N 3 -CAR-NK) cells, including recognition specificity, migration efficiency, and cytotoxic activity. Herein, ManNAl-SeNPs with ultra-sensitive responsiveness of diselenide bonds, in the acidic TME, diselenide bond releases seleninic acid, acting as an immune checkpoint inhibitor while augmenting CAR-NK cells cytotoxicity. In vivo, the combination of ManNAl-SeNPs with N 3 -CAR-NK cells significantly increased targeting capacity and invasiveness. This study presents a TME-responsive nanoplatform with artificial bio-orthogonal combination strategy that effectively enhance the migratory ability and accumulation of CAR-NK cells for potent antitumor therapy.
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Cell Chemical Biology
·
2020
·
IF 7.739
Bo Zhang,Yan Wang,Shenlong Huang,Jiaqi Sun,Min Wang,Wenxiao Ma,Yanbo You,Ling Wu,Jin Hu,Wei Song,Xudong Liu,Shengjie Li,Hua Chen,Guisheng Zhang,Lihe Zhang,Demin Zhou,Lingjun Li,Xuan Zhang
Summary Chimeric antigen receptor (CAR)-T-based therapeutics are a breakthrough in cancer treatment; however, they are hampered by constitutive activation, which leads to worrisome side effects. Engineering CAR-T cells to be as tightly controllable as possible remains a topic of ongoing investigation. Here, we report a photoswitchable approach that uses a mediator for the at-will regulation of CAR-T cells. This mediator carries dual folate and fluorescein isothiocyanate moieties tethered by an ortho-nitrobenzyl ester photocleavable linker. CAR-T cells were shown to be highly cytotoxic to targeted cells only in the presence of the mediator and acted in a dose-dependent manner. The toxicity of CAR-T cells can be rapidly terminated by cleavage of the mediator, and the effects of CAR-T cells can be activated again by resupplementation with the mediator without compromising tumor therapy. The approach described here provides a direction for enhancing the controllability of CAR-T cells and can likely be applied in other immunotherapies.
研究领域:
免疫疗法
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癌症研究
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分子生物学
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生物医学工程
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NATURE MATERIALS
·
2026
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IF 38
Cao Qiannan,Yao Yingli,Zheng Wenming,Liu Hongqian,Jiang Mingxia,Xie Dayang,Zhang Siting,Su Pijun,Yuan Huilin,Chen Xiaoyuan,Fang Huapan,Tian Huayu
The clinical success of chimeric antigen receptor (CAR) T cell therapy requires scalable, non-invasive strategies for in vivo T cell engineering. Although mRNA delivery offers a promising alternative, lipid-nanoparticle-based carriers show limited efficiency for in vivo T cell transfection and typically require antibody conjugation. Here we report an inherent T cell-activating polymer–lipid nanoparticle that enables ligand-free, efficient mRNA transfection and activation of T cells in vivo. This mRNA delivery vehicle, composed of p -toluenesulfonyl arginine (RT)-modified oligoethylenimine-based lipid nanoparticles (ERTLNPs), preferentially mediated mRNA transfection in the spleen following systemic administration. Without exogenous stimulation, ERTLNPs intrinsically activated T cells, triggering robust mRNA expression and proliferation. Mechanistically, ERTLNPs engaged the PI3K/AKT/mTOR signalling axis to reprogram T cell metabolism, promoting expansion and restraining exhaustion. The systemic delivery of mRNA encoding fibroblast activation protein CAR via ERTLNPs contributed to the in situ generation of functional CAR T cells, which efficiently eliminated pathological fibroblasts in models of cancer and fibrosis, with minimal off-target effects. This ligand-free, metabolically reprogramming mRNA delivery system provides a clinically translatable approach for in vivo CAR T cell generation.
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Cell Host & Microbe
·
2026
·Vol. 34
·期 2
·212-229
·
IF 18.7
Yulin Zhang,Jianyu Shen,Yu Xu,Fan Feng,Xu Han,Kaiyan Xi,Zezheng Fang,Yi Zhang,Mingrui Wang,Zixu Wang,Pengfei Zhu,Qikang Zhang,Zhiqiang Li,Baichuan Liu,Zeyue Cao,Chaoqun Wang,Qianen Xu,Yang Yu,Chengpeng Sun,Xinrui Wang,Jingjing Wang,Jiaojiao Pang,Zimei Wu,Huimin Geng,Ahmet Acar,Thomas Daubon,Wenli Zhang,Yanrong Zhang,Xingang Li,Yuguo Chen,Shilei Ni,Xinyi Jiang
Glioblastoma (GBM) remains a highly lethal form of cancer due to its molecular heterogeneity and the immunosuppressive microenvironment surrounding the tumor. Here, we report a modular immunotherapy platform characterized by its flexibility to simultaneously target multiple antigens. Specifically, we utilize engineered E. coli Nissle to colonize tumors and produce bispecific engagers that simultaneously target EGFRvIII and interleukin (IL)-13Rα2. These tags direct in situ -reprogrammed chimeric antigen receptor (CAR) macrophages, which are edited using nanoparticles and delivered within a shear-thinning hydrogel, to execute targeted phagocytosis. This probiotic-macrophage crosstalk eliminates tumor cells while converting protumor M2 macrophages into immunostimulatory M1 effectors. In aggressive orthotopic GBM mouse models, this strategy achieves 83% survival at the 120-day endpoint, representing a 5-fold improvement over single-target controls and establishing durable immunological memory that effectively combats recurrence. By functioning as multifunctional immune hubs, this platform offers a versatile framework designed to overcome the antigenic complexity of solid tumors.
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Cell Reports Medicine
·
2026
·
IF 14
Wenyan Zhao,Xin Zhou,Xingli Zhao,Hao Tian,Yang Su,Shanlan Zhao,Min Liu,Qiao Zhang,Lin Chen,Xiaochen Li,Di Liu,Junxuan Li,Lang Li,Yanhong Wang,Xingtong Li,Jin Yan,Wen Chen,Bing Liu,Chuhong Zhu,Wen Zeng
Renal fibrosis is a common outcome of chronic kidney disease (CKD), forming a fibrotic niche characterized by fibroblast activation and vascular rarefaction. Currently, there are no effective treatment strategies targeting fibrotic niche. Here, we show that chimeric antigen receptor-modified M2 macrophages (CAR-M2) targeting FAP and secreting interleukin (IL)-4 are delivered via an injectable HAMA-CS hydrogel beneath the renal subcapsule and attenuate renal fibrosis while promoting renal revascularization. The single-cell RNA sequencing reveals the heterogeneity and interaction of stroma and endothelial cells (ECs). A fibrosis-related Cxcr2 + EC subset is identified, and its specific depletion effectively mitigates renal fibrosis. Further results reveal that CAR-M2 can release matrix metalloproteinase 2 (MMP2) in close proximity to activate retinoid X receptor alpha (Rxra) in the Cxcr2 + ECs and further triggers its mitochondrial autophagy, leading to apoptosis. Our research provides innovative strategies and proof of principle for the immunotherapy of organ fibrosis.
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Frontiers in Immunology
·
2026
·
IF 7
Zhiying Chen,Muya Zhou,Xiaoyu Li,Yuqi Zhao,Zhengling Wang,Jinhua Hu,Jialu Hong,Shenrui Zhou,Feiyan Pan,Zhigang Hu,Lingfeng He,Tao Gao,Xiaodong Jiang,Zhiqiang Wang,Zhigang Guo
Background CAR-T therapy is limited by off-target sequestration in liver, spleen, and lungs, which reduces tumor delivery and risks systemic toxicity. Genetic engineering approaches are complex and carry safety concerns, necessitating efficient non-genetic strategies to optimize CAR-T biodistribution. Purpose We developed red blood cell membrane–chimeric liposomes (Rlip) as a biomimetic coating system to non-genetically modify CAR-T cells, aiming to enhance immune evasion, prolong circulatory persistence, and redirect trafficking toward tumors while preserving intrinsic effector function. Methods Rlip-CAR-T cells were prepared via simple incubation. In vitro characterization assessed coating stability, CD47-mediated macrophage resistance, phenotype preservation, and antigen-specific cytotoxicity. In vivo studies evaluated biodistribution, tumor infiltration, and efficacy in Nalm-6 systemic leukemia and 1806-luc subcutaneous ovarian cancer models. Results Rlip coating stably presented CD47, functionally impairing macrophage phagocytosis and enhancing peripheral persistence without altering memory subsets, activation markers, or cytotoxicity. Rlip-CAR-T cells demonstrated markedly reduced off-target organ accumulation and increased intratumoral enrichment in both models, with superior tumor control and prolonged survival observed in the leukemia model. Conclusions Rlip surface engineering represents a universal, clinically translatable strategy to overcome CAR-T biodistribution barriers. By integrating erythrocyte-mimetic immune evasion with optimized tumor delivery, this approach improves CAR-T cell accumulation at tumor sites across hematologic and solid malignancies.
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BIOMATERIALS
·
2026
·
IF 13.6
Yuxin Qian,Wentao Wang,Mingzhe Xin,Haonan Ding,Yi Shuai,Zelong Hu,Xuwen Wang,Shijia Huang,Rui Mu,Ming Zhang,Lei Jin
Radiotherapy for head and neck cancer frequently induces severe radiation-induced oral mucositis (RIOM), in which excessive reactive oxygen species (ROS), defective macrophage efferocytosis, and persistent inflammation form a self-amplifying pathological loop that delays mucosal repair. Current symptomatic treatments are insufficient to simultaneously suppress oxidative stress and restore immune-mediated clearance of damaged cells. Here, we developed a detachable microneedle patch with ROS-responsive tips (PTC MN) for localized in situ macrophage programming within RIOM lesions. The PTC MN was fabricated from a PPBA-TA-PVA hydrogel matrix, which combines intrinsic ROS-scavenging capacity with oxidative stress triggered degradation, and loaded with engineered hybrid nanovesicles (HLENs-CAR) carrying a plasmid encoding CAR-ectoCRT-IL-4. This design enabled local delivery of gene-loaded nanovesicles, macrophage-targeted genetic programming, and sustained retention of the therapeutic payload in the injured mucosa. In a murine RIOM model, PTC MN accelerated mucosal epithelial regeneration, reduced oxidative stress and inflammatory infiltration, enhanced reparative macrophage responses, and attenuated fibrosis-associated tissue remodeling. Functionally, the platform enhanced macrophage efferocytosis, promoted IL-4-associated reparative polarization, and shifted the lesion microenvironment toward inflammation resolution and tissue regeneration. Collectively, this study establishes a smart in situ immunomodulation strategy that integrates ROS-responsive microneedle delivery with CAR-macrophage programming, providing a potential therapeutic paradigm for refractory mucosal injury.
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Catalysis Science & Technology
·
2025
·
IF 4.2
Chuqiao Song,Wei Cheng,Xiaojie Wu,Shufang Zhao,Ying Tang,Xin Tang,Yao Xu,Lili Lin,Siyu Yao
The one-pot hydrodeoxygenation of lignin-derived (alkyl)-guaiacols to (alkyl)-cyclohexanols with high selectivity is an attractive process for biomass conversion. However, designing catalysts that preferentially cleave etheric CAr–O(R) bonds over hydrogenating aromatic rings under mild conditions remains a significant challenge. In this study, we explore the structure sensitivity of supported Ru catalysts with varying particle sizes (0.6–7.5 nm) and identify the optimal catalyst for selective hydrodeoxygenation. Using a catalyst with 1.5 nm Ru particles, we achieve a ∼95% yield of cyclohexanol from guaiacol under relatively mild conditions (190 °C, 5 bar H2). In situ DRIFTS analysis reveals that the cleavage of CAr–OCH3 bonds occurs preferentially over aromatic ring hydrogenation on the 1.5 nm Ru particles, minimizing side reactions and enhancing cyclohexanol selectivity.
研究领域:
化学工程
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催化材料科学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 21
·11695
·
IF 4.9
Jiachen Shi,Zeping Ji,Xu Yao,Yujie Yao,Chengyun Li,Qijun Liang,Xiaohui Zhang
Heat shock protein 90 (HSP90) is recognized for its protective effects against heat stress damage; however, the specific functions and underlying molecular mechanisms of HSP90 in heat-stressed cardiomyocytes remain largely unexplored, particularly in tropical species. In our study, Wenchang chickens (WCCs) were classified into two groups: the heat stress survival (HSS) group and the heat stress death (HSD) group, based on their survival following exposure to heat stress. Heat stress resulted in significant cardiomyocyte damage, mitochondrial dysfunction, and apoptosis in the HSD group, while the damage was less pronounced in the HSS group. We further validated these findings in primary cardiomyocytes derived from Wenchang chickens (PCWs). Additionally, heat stress was found to upregulate Pink1/Parkin-mediated mitophagy, which was accompanied by an increase in HSP90 expression in both cardiomyocytes and PCWs. Our results demonstrated that HSP90 overexpression enhances PINK1/Parkin-mediated mitophagy, ultimately inhibiting apoptosis and oxidative stress in heat-stressed PCWs. However, the application of Geldanamycin (GA) reversed these effects. Notably, we discovered that HSP90 interacts with Beclin-1 through mitochondrial translocation and directly regulates mitophagy levels in PCWs. In summary, we have elucidated a novel role for HSP90 and mitophagy in regulating heat stress-induced acute cardiomyocyte injury.
研究领域:
分子生物学
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细胞生物学
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应激生理学
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兽医学
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JOURNAL OF POROUS MATERIALS
·
2024
·
IF 2.5
Pawar Chander Amgoth,Luo David Xu,Rokkala Divya,Bura Raju,Bhagyalaxmi Gundeti,Rani Rampilla Sudha,Mannam Krishna Veni,Babu Kothamasu Suresh
We present, a facile method for the synthesis of block co-polymer (BCP) of [(PLA)- b -(Car)], (PLA-Poly Lactic acid and Car-Carbazole). BCP results in the design and development of cone and ice-cream cup-shaped frustums with nanoscale porosity for bio-sensing and drug delivery applications. [(PLA)- b -(Car)] was conjugated through condensation polymerization between amine proton and hydroxyl groups of PLA and Car. Thermoplastic PLA is responsible for desired size, shape, and porosity over the surface. The size, shape, and morphology of the [(PLA)- b -(Car)] are tunable based on suitable solvents and thermal treatment. Interestingly, design of nanoporous hollow (half-broken coconut type) capsules has been carried out without using any precursors and surfactants. Synthesis of [(PLA)- b -(Car)] has been confirmed through the Fourier transform infrared (FTIR), nuclear magnetic resonance ( 1 H NMR). However, the morphology and surface properties of capsules were confirmed through field emission scanning electron microscopy (FE-SEM), Bruner Emmett Teller (BET), and atomic force microscopy (AFM) characterizations. The capsule size ranges from ~ 200 nm to 1 μm (in diameter) and porosity scales from ~ 60 to 80 nm. The hollow and porous surface of the capsules with biosensing and drug delivery applications can be considered as a unique and novel characteristic property of our invention. This kind of novel cone and ice cream cup-shaped hollow frustums can be used as a stimuli-responsive catalytic activity through the fluorescence measurement of cysteine and gold nanoparticle [(Cys)-(Au + )] for enhanced payload and biomedical applications.
研究领域:
材料科学
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生物医学工程
·
化学工程
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Translational Cancer Research
·
2025
·Vol. 14
·期 10
·6454
·
IF 1.7
Jiaxuan Zhao,Han Wu,Zhe Sun,Yeting Cui,Nan Liu,Yixuan Wang,Youyong Wang,Jiangzhou Shi,Tongcun Zhang
Background Chimeric antigen receptor T cell (CAR-T) therapy targeting cluster of differentiation 19 (CD19) has shown promise in treating B-cell acute lymphoblastic leukemia (B-ALL), but the long-term efficacy of CD19-targeted CAR-T therapy remains limited. Programmed cell death protein 1 (PD-1), an inhibitory receptor on activated T cells, engages programmed death ligand 1 (PD-L1) in the tumor microenvironment, suppressing CAR-T cell function by impairing key signaling pathways. To address this limitation, we investigated the effect of short hairpin RNA (shRNA)-mediated PD-1 knockdown on alleviating CAR-T cell exhaustion, preserving memory phenotype, and enhancing the long-term efficacy of CD19-targeted CAR-T cells. Methods To overcome this limitation, we employed shRNA to achieve PD-1 knockdown in CD19-targeting CAR-T cells. Following screening multiple shRNA candidates, we assessed the cytotoxicity, cytokine secretion, and proliferation of PD-1 knockdown CAR-T cells. Their memory phenotype, exhaustion marker, and cytolytic function were further evaluated after repeated antigen stimulation. Therapeutic efficacy and safety were validated in NOD.Cg-PrkdC scid Il2rg tm1 /Vst (NPG) mice. Results PD-1 knockdown significantly enhanced CAR-T cell cytotoxicity and persistence against PD-L1+ RAJI (human Burkitt’s lymphoma cell line) cells. After three rounds of antigen stimulation, PD-1 knockdown CAR-T cells sustained cytotoxic activity, retained a memory-like phenotype, and displayed attenuated exhaustion markers. In vivo , they prolonged survival without inducing cytokine release syndrome (CRS), indicating improved efficacy and safety. Conclusions PD-1 knockdown mitigates tumor-induced T-cell exhaustion and represents a promising strategy to enhance the durability and potency of CAR-T cell therapy in cancer treatment.
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