Biomaterials Research
·
2025
·
IF 9.6
Xiao-Kai Chi,Hai-Rui Zhang,Jing-Jing Gao,Jin Su,Yong-Zhong Du,Xiao-Ling Xu
Immunogenic cell death, triggered by photothermal therapy or specific chemotherapy, strives to establish a positive feedback loop in cancer immunotherapy. This loop is characterized by the rapid release of antigens and adenosine triphosphate (ATP), ultimately leading to accelerated T cell infiltration. However, this loop is hindered by T cell exhaustion caused by adenosine originating from ATP and glucose deprivation in the immunosuppressive microenvironment. To overcome this challenge, we developed a pH-low insertion peptide-functionalized mesoporous-polydopamine-based nanoadjuvant that incorporates adenosine deaminase and doxorubicin (termed as PPMAD). PPMAD aimed to overcome T cell exhaustion by reducing adenosine consumption and providing an alternative carbon source for CD8+ T cell function during glucose starvation. First, PPMAD triggered the burst release of antigens and ATP through photothermal therapy and doxorubicin-induced immunogenic cell death, culminating in the expedited infiltration of T cells. Second, adenosine deaminase depleted adenosine, reducing immunosuppressive agents and generating abundant inosine, which served as an alternative carbon source for CD8+ T cells. By implementing this “reducing suppression and broadening sources” strategy, we successfully overcome T cell exhaustion, greatly enhancing the effectiveness of cancer immunotherapy both in vitro and in vivo. Our findings highlighted the positive feedback loop between on-demand photothermal therapy, chemotherapy immunotherapy, and achieving complete tumor response.
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ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yiping Wang,Yang Jin,Yanjun Zhong,Pan Zhu,Jun Li
Iron based Prussian blue analogues (Fe-PBA) hold significant promise cathode materials for sodium ion batteries due to their low cost and desirable electrochemical properties. However, their practical application is often hindered by the presence of vacancy defects and issues of oxidation that arise during the material preparation process. To overcome these challenges, this study introduces an innovative T-shaped collision microreactor aimed at promoting a uniform concentration field, narrowing the gap between material mixing rate and reaction rate, and providing an oxygen-free environment for the synthesis of Fe-PBA. Employing this microreactor, Fe-PBAs were synthesized with a meticulous approach that led to a material possessing a well-defined morphology and a stoichiometry of Na1.54Fe[Fe(CN)6]0.93. The material exhibited a notable reduction in vacancy defects and minimized oxidation levels. Upon electrochemical evaluation, the Fe-PBA crafted within the microreactor demonstrated an impressive specific capacity of 94.1 mAh/g at a current density of 0.5 C and showcased a long-term cyclability with 72.6% capacity retention over 2000 cycles. Comparative analysis revealed that the structural and electrochemical properties of Fe-PBA prepared in the microreactor outperformed those of samples prepared using traditional reactors. This work provides a new approach for the continuous and stable fabrication of high-performance battery cathode materials.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Si-Yi Han,Hong-Fu Zhao,Zi-Ying Zhao,Jing-Zhi Yu,Ying-Hua Zhang,Zhi-Shen Mu
Food-derived protein peptides with γ-aminobutyric acid transaminase (GABA-T) inhibitory activity possess the promising ability to alleviate anxiety and have become a market focus. This study prepared casein hydrolysate with valid GABA-T inhibitory activity using ultrasound-assisted enzymatic hydrolysis and obtained novel GABA-T inhibitory peptides through isolation and purification. The results demonstrated that ultrasonic pretreatment significantly improved the casein hydrolysis efficiency, enhanced GABA-T inhibitory activity by 19.32%, and allowed retention of 42.37% of the initial inhibitory activity after gastrointestinal digestion. Through peptidomics analysis, five novel GABA-T inhibitory peptides were identified from casein hydrolysate, including FFVAPFPE, VYPFPGPIPN, HLPLPL, FLPYPY, and WQVL (2.79 ± 0.14 to 8.49 ± 0.26 mM). Molecular docking results revealed that these five peptides bind to GABA-T through hydrogen bonds and hydrophobic interactions, with the Arg422 residue potentially serving as the key active site for GABA-T inhibition. This study demonstrates significant potential for both the high-value utilization of casein and the development of antianxiety functional foods targeting GABA-T.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yaqian He,Zichuang Xu,Yaqian Yan,Jiajun Gao,Xuwu Zhang,Yuchu He,Qingzhi Luo,Desong Wang,Dawei Gao
The crucial challenge of nanodrug systems is their low transfer efficiency, which requires overcoming transmission resistance due to tumour accumulation and intratumoural penetration. In this study, we propose a synergistic strategy involving ‘pioneer’ T cells and ‘main force’ piezo-nanozymes to enhance the ability of T cells and nanodrugs to simultaneously target tumours with high specificity and achieve enhanced immunotherapy. Herein, a mature dendritic cell (DC) membrane was used to encapsulate the piezo-nanozyme MoS 2 to form nanodrugs (MDMs). On the basis of the lymphatic homing ability of mature DCs, MDMs can accumulate in tumour-draining lymph nodes to activate T cells and rivets on T cells. T cells subsequently serve as ‘pioneers’, overcoming circulatory barriers and leading to MDM accumulation in tumours. Furthermore, the piezo-nanozyme MoS 2 acts as the ‘main force’ for reducing tumour interstitial fluid pressure through piezocatalysis, thereby reducing intratumoural penetration resistance and increasing the permeation efficiency of T cells and nanodrugs. Piezocatalysis initiates immunogenic cell death, further enhancing the efficacy of T-cell immune responses, which not only clear the primary tumour but also inhibit tumour metastasis. This study provides a novel strategy and theoretical basis for overcoming biological barriers and improving the effects of chemotherapy and immunotherapy.
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RSC Advances
·
2024
·Vol. 14
·期 49
·36804-36815
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IF 3.9
Yi Zheng,Haochen Liu,Bingkun Lu,Muchen Dong,Xinhai Wang
Dry eye syndrome (DES) is a prevalent condition linked to oxidative stress from Orthokeratology (OK) lens use, causing significant discomfort and impacting quality of life. Herein, this study investigates the role of Reactive Oxygen Species (ROS) in modulating T cell responses, particularly Th17 cells and IL-17A production, which are central to DES pathogenesis. We propose a novel therapeutic strategy using ceria nanoparticles (CeNPs) for ocular ROS clearance, hypothesized to attenuate Th17 activation and IL-1β and IL-17A production, thereby reducing DES symptoms. We developed a hybrid coating for OK lenses using Schiff base reactions to link tannic acid with CeNPs, aiming to neutralize ROS and mitigate inflammation. This approach could offer a transformative treatment for DES, especially among OK lens users. In comparison to existing therapies, our approach demonstrated a 70% reduction in corneal inflammation markers and a 2.5-fold increase in tear secretion, offering a transformative treatment for DES, especially among OK lens users.
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Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·1-17
·
IF 52.7
Tang Yu,Luo Zhiyuan,Ma Zhanni,Han Lingling,Zhou Yurong,Liang Tianci,Yang Kangsen,Zhao Lei,Chen Xiaoyuan,Zhang Pengfei
The variety and functionality of current clinical vaccine adjuvants remain limited. Conventional aluminum-based adjuvants predominantly induce Th2-biased humoral immunity but exhibit a limited capacity to elicit Th1-mediated cellular immune responses, particularly tumor antigen-specific cytotoxic CD8 + T lymphocytes (CTLs), which are essential for effective cancer vaccine performance. Inspired by natural biomolecular condensates, we developed a versatile noncovalent protein self-assembly strategy distinct from traditional approaches requiring structural domain modifications or bifunctional crosslinkers. Our methodology employs amphiphilic molecules (sodium myristate/SMA and sodium dodecyl thiolate/SDT) as molecular bridges to mediate protein‒protein interactions through hydrophobic forces and disulfide bond formation. This process generates nanoscale protein condensate (PCD) vaccines with exceptional stability. As a novel adjuvant system, these synthetic condensates significantly enhance antigen cross-presentation by optimizing key parameters: antigen loading capacity, lymph node targeting, cytosolic delivery, and lysosomal escape. Consequently, they induce robust antigen-specific CTL responses and humoral immunity, demonstrating potent antitumor efficacy. Importantly, we found that the synthetic protein condensate (PCD) alone can act as a nanoadjuvant. By increasing mitochondrial membrane permeability, PCD induces mitochondrial DNA leakage into the cytosol, activating the cGAS‒STING pathway and promoting DC maturation. This safe and scalable platform eliminates the need for complex covalent modifications or genetic engineering, and it facilitates the design of diverse modular antigens, including neoantigens and viral antigens. Given its straightforward manufacturing process and superior immunogenicity, this synthetic PCD vaccine adjuvant has significant potential for clinical application and translation.
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BIOMATERIALS
·
2024
·
IF 12.8
Bo Zhang,Guidong Gong,Yunxiang He,Jialing Liu,Bo Wang,Yifei Li,Jie Fang,Zhihe Zhao,Junling Guo
Global aging heightens the risk of oral disorders, among which periodontitis is the major cause of tooth loss in the aging population. The regeneration of damaged periodontal hard tissue is highly challenging due to the existence of the refractory local inflammation. Owing to the potent anti-inflammatory capabilities, regulatory T cells hold great promise in immunotherapies for tissue regeneration. However, the transferred regulatory T cells can alter their phenotypes and functions in local inflammatory milieu, significantly impairing their therapeutic efficacy. Herein, we introduce a novel regulatory T cell-based nanobiohybrid system bearing polyphenol-functionalized rapamycin nanocomplexes. The sustained in situ release of immunosuppressant rapamycin from the cell-attached nanocomplexes maintains the anti-inflammatory phenotype of regulatory T cells in the inflammatory milieu. The synergistic actions of the anti-inflammatory cytokines secreted and the immunosuppressant released guide a pro-resolving polarization of macrophages and enhance osteogenic differentiation of bone marrow-derived stromal cells. The stabilized phenotype of the regulatory T cells dramatically promoted the resolution of periodontal inflammation and the repair of the hard tissue (alveolar bone) in vivo . Overall, these studies highlight a potent regulatory T cell-based nanobiohybrid therapy to treat periodontitis by modulating periodontal immune microenvironment.
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Nature Biomedical Engineering
·
2023
·Vol. 7
·期 9
·1129-1141
·
IF 28.1
Li Xianlei,Gong Ningqiang,Tian Falin,Zhang Shangkun,Zhang Yuxuan,Wang Yufei,Qing Guangchao,Wang Yongchao,Li Fangzhou,Xu Yihui,Zhang Linlin,Wang Jinjin,Ni Qiankun,Gan Yaling,Gu Chaojiang,Jiang Huaidong,Huang Xingxu,Shi Xinghua,Zhang Tongcun,Wu Yan,Liang Xing-Jie
The infusion of chimaeric antigen receptor (CAR) T cells can trigger the release of life-threatening supraphysiological levels of pro-inflammatory cytokines. However, uncertainty regarding the timing and severity of such cytokine release syndrome (CRS) demands careful monitoring of the conditions required for the administration of neutralizing antibodies. Here we show that a temperature-sensitive hydrogel conjugated with antibodies for the pro-inflammatory cytokine interleukin-6 (IL-6) and subcutaneously injected before the infusion of CAR-T cells substantially reduces the levels of IL-6 during CRS while maintaining the therapy’s antitumour efficacy. In immunodeficient mice and in mice with transplanted human haematopoietic stem cells, the subcutaneous IL-6-adsorbing hydrogel largely suppressed CAR-T-cell-induced CRS, substantially improving the animals’ survival and alleviating their levels of fever, hypotension and weight loss relative to the administration of free IL-6 antibodies. The implanted hydrogel, which can be easily removed with a syringe following a cooling-induced gel–sol transition, may allow for a shift in the management of CRS, from monitoring to prevention.
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Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2024
·
IF 1.4
Xie Huilong,Fu Yunrong,Lin Zhisheng,Wang Jiayi,Wu Jingyu,You Xiuhua,Xie Jieming
This study explores the synergistic effect of T-CUS 245C combined with cyclosporin A, and its possible mechanism. T-CUS 245C is an immunotoxin conjugated with tastuzumab and recombinant cucurmosin 245C (CUS 245C ). Cyclosporin A is a calcium antagonist mainly used as an immune-suppressive agent, which enhances the cytotoxicity of immunotoxins through an unknown mechanism. The sulforhodamine B assay, flow cytometry, DNA fragmentation apoptosis assay, and western blot analysis were used to evaluate the synergistic effects of cyclosporin A combined with T-CUS 245C on proliferation inhibition and apoptosis induction in SK-OV-3 ovarian cancer cells with HER-2-overexpressing. Meanwhile, using confocal microscopy and flow cytometry, the effect of cyclosporin A on the intracellular distribution of T-CUS 245C was observed and quantified. The results of this study showed that the combination index of cyclosporin A combined with T-CUS 245C is less than 0.7, indicating that cyclosporin A significantly enhances the proliferation inhibition and apoptosis induction induced by T-CUS 245C in SK-OV-3 cells. The confocal microscopy and flow cytometry results show that cyclosporin A effectively increases the dispersion of T-CUS 245C in the cytoplasm by promoting the endolysosomal escape. This study demonstrates that cyclosporin A combined with T-CUS 245C has a synergistic anticancer effect, by facilitating the release of T-CUS 245C in the intracellular space. Graphical Abstract
研究领域:
肿瘤学
·
细胞生物学
·
药理学
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Journal of Functional Foods
·
2020
·
IF 3.701
Liu Tang,Xiaolei Li,Liping Wan,Huiling Wang,Qianting Mai,Zixin Deng,Hong Ding
The present research was designed to evaluate the protective effects and underlying mechanisms of different ratios of linoleic acid (LA) and α-linolenic acid (ALA), two essential polyunsaturated fatty acids (PUFAs) fatty acids, on atopic dermatitis (AD)-like skin lesions induced by 2, 4-dinitrofluorobenzene (DNFB). The dorsal flank and ear pinnas of mice were sensitized and challenged with DNFB for four weeks in order to establish AD model. Simultaneously, the mice were orally administered different ratios of LA/ALA (v/v; 4:1 or 1:1), or dexamethasone (Dex; 0.1 mg/kg). Results showed that different LA/ALA ratios, especially a ratio of 4:1 treatment, could effectively ameliorate DNFB-induced skin lesions, ear edema, scratching behavior and skin inflammation, as reflected by the reduced inflammatory blood cells, IgE serum levels, and skin levels of the pro-inflammatory lipid mediators, including PGE 2 and LTB 4 . These findings were further confirmed by skin pathological examination. Moreover, LA/ALA administration markedly suppressed the proliferation and infiltration of T cells, the production of T helper cell type 1 (Th1), Th2 and Th17 cytokines in dorsal skin and serum of DNFB-treated mice. Western blotting and immunohistochemistry staining revealed that LA/ALA downregulated the protein expressions of JAK2 and STAT4, and thus reducing the synthesis of type Th1 cytokine IFN-γ. Taken together, these results suggest that optimal nutrition ratio of LA/ALA has beneficial effects on AD-like symptoms, which provide theoretical basis for its therapeutic potential in the clinical prevention and treatment of AD.
研究领域:
免疫学
·
营养学
·
皮肤病学
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ENZYME AND MICROBIAL TECHNOLOGY
·
2022
·
IF 3.705
Cheng Zeng,Xiangqing Ji,Yu Shi,Siyu Mu,Yicheng Huang,Meiqiao Zhong,Yan Han,Cuicui Duan,Xiaolei Li,Dan Li
To develop a new method for enzymatic preparation of minor ginsenosides , T. stercorarium β-glucosidase (Tsbgl) was characterized and its activities of deglycosylation towards natural ginsenosides were examined. The substrates of 1 mmol l −1 were incubated with the enzyme of 38.3 U ml −1 at 65 ℃ and pH 5.0. The K m values of Tsbgl for ginsenosides Rb 1 , Rg 1 and p NPG were 0.37 ± 0.03, 3.26 ± 0.19, and 1.24 ± 0.03 mmol l −1 , and the V max values were 183.63 ± 7.15, 85.03 ± 4.90, and 117.66 ± 1.96 μmol mg −1 min −1 , respectively. The molar conversion of ginsenosides Rb 1 , Rb 2 , Rb 3 , Rc, Re, Rg 1 , and Rf by Tsbgl within 6 h was 100%, 50.1%, 42.7%, 92.0%, 57.3%, 67.9%, and 76.8%, respectively. The yield of aglycone protopanaxadiol was 35.5 μmol l −1 h −1 for Rb 1 , while the yields of aglycone protopanaxatriol were 64.2 and 70.4 μmol l −1 h −1 for Rg 1 and Rf. Tsbgl with good organic solvent tolerance, mild reaction conditions and broad substrate specificity , could completely remove all outer glucosyls at the C-3 and C-20 hydroxyls of protopanaxadiol-type ginsenosides, and the C-6 and C-20 hydroxyls of protopanaxatriol-type ginsenosides through various pathways, providing a specific and efficient way to produce minor ginsenosides.
研究领域:
生物化学
·
药理学
·
酶学
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Cell Reports Medicine
·
2025
·
IF 10.6
Cheng Gao,Ruifeng Luo,Cheryl H.T. Kwong,Jinwei Liu,Mian Tang,Beibei Xie,Tianshun Duan,Ruibing Wang
The effectiveness of whole tumor cell vaccines prepared by traditional inactivation methodology is often hindered by insufficient immunogenicity. Here, we report development of a cancer vaccine through the intracellular gelation of tumor cells, combined with CD47 blockade and damage-associated molecular pattern (DAMP) exposure, for effective tumor prevention and treatment. Intracellular hydrogelation preserves the morphology and antigenicity of tumor cells. CD47 blockade and DAMP exposure synergistically enhance the “eat me” signals and inhibit the “don’t eat me” signals on tumor cells, significantly improving their immunogenicity. In the context of tumor prevention and treatment of pre-existing tumors, this vaccine polarizes CD4 + T cells toward a T H 1 phenotype, reduces regulatory T cells and T cell exhaustion, and elicits a robust tumor-antigen-specific T cell response. When combined with an immune checkpoint inhibitor, this vaccine demonstrates enhanced efficacy in eradicating established tumors. The successful application of this vaccine using ascites and subcutaneous tumor cells supports the feasibility of developing personalized whole tumor cell vaccines for diverse tumor types.
研究领域:
肿瘤学
·
免疫学
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