Exploration
·
2025
·
IF 22.5
Panpan Xue,Tingjie Bai,Huilan Zhuang,Angelo H. All,Shuangqian Yan,Xuemei Zeng
Stimulating the immunogenic cell death (ICD) by chemical and photothermal agents triggers antitumor immune responses to tumor treatments. However, the abnormal cholesterol accumulation in cancer cells promotes tumor survival and metastasis, while the high concentration of cholesterol in the tumor microenvironment will result in T exhaustion. Herein, a cholesterol-regulable nanoliposome (ictLipo) that encapsulated with IR806, tirapazamine, and cholesterol oxidase (ChOx) was fabricated to boost chemo/photothermal-activated ICD and antitumor immune responses. Specifically, the released ChOx oxidizes cholesterol, accompanied by oxygen consumption and ATP reduction. Whereupon, tumoral anabatic hypoxia activates the toxicity of tirapazamine while ATP reduction strengthens photothermal therapy of the IR806 by suppression of HSP70. We found that this interactive strategy evokes robust ICD and reverses T-cell exhaustion. When combined with the immune checkpoint blockade, ictLipo can efficiently restrain breast cancer metastasis in two tumor models. The interactive strategy sheds new light on the immunological facet of cholesterol metabolism and may provide a new therapeutic strategy against breast cancer.
研究领域:
癌症免疫治疗
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纳米医学
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肿瘤微环境
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免疫代谢
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光热治疗
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 32
·2203523
·
IF 17.521
Ming Shen,Chuanrong Chen,Qianqian Guo,Quan Wang,Jinghan Liao,Liting Wang,Jian Yu,Man Xue,Yourong Duan,Jiali Zhang
T-cell engagers (TCEs) represent a breakthrough in hematological malignancy treatment but are vulnerable to antigen escape and lack a vaccination effect. The “immunologically cold” solid tumor presents substantial challenges due to intratumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Here, a methoxy poly(ethylene glycol) (mPEG)-masked CD44×PD-L1/CD3 trispecific T-cell nanoengager loaded with the STING agonist c-di-AMP (CDA) (PmTriTNE@CDA) for the treatment of triple-negative breast cancer (TNBC) is rationally designed. PmTriTNE@CDA shows tumor-specific accumulation and is preferentially unmasked in response to a weakly acidic TME to prevent on-target off-tumor toxicity. The unmasked CD44×PD-L1/CD3 trispecific T-cell nanoengager (TriTNE) targets dual tumor-associated antigens (TAAs) to redirect CD8+ T cells for heterogeneous TNBC lysis while achieving PD-L1 blockade. PmTriTNE synergized with CDA to transform the cold tumor into a hot tumor, eradicate the large established TNBC tumor, and induce protective immune memory in a 4T1 orthotopic tumor model without causing obvious toxicity. PmTriTNE@CDA shows potent efficacy in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. This study serves as a proof-of-concept demonstration of a nanobased TCEs strategy to expand therapeutic combinations that previously could not be achieved due to systemic toxicity with the aim of overcoming TNBC heterogeneity and immunotherapy resistance.
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
ACS Pharmacology & Translational Science
·
2024
·
IF 4.9
Jing-Jing Du,Shi-Hao Zhou,Jin Liu,Xing-Yuan Zhong,Ru-Yan Zhang,Wen-Xiang Zhao,Yu Wen,Zhen-Hong Su,Zheng Lu,Jun Guo
The tumor-associated antigen MUC1 is an attractive target for immunotherapy, however, its weak immunogenicity limits the induction of antitumor immune responses. To overcome this limitation, in this study, MUC1 glycopeptide was covalently linked with a diphtheria toxin-derived T-helper epitope (DT331–345). Subsequently, the resulting DT-MUC1 glycopeptide was physically mixed with natural killer T cell agonist αGalCer to explore their immunomodulatory synergy. Biological results demonstrated that compared to MUC1+αGalCer and DT-MUC1 groups, the specific IgG antibody titer of DT-MUC1+αGalCer group increased by 189- and 3-fold, respectively, indicating that the diphtheria toxin-derived T-helper epitope synergistically enhanced MUC1 immunogenicity with αGalCer. Moreover, the DT-MUC1+αGalCer vaccine induced potent cellular immune responses and significantly inhibited the growth of B16-MUC1 tumors in vivo. Furthermore, it was found that the anti-MUC1 IgG antibody titer induced by DT-MUC1+αGalCer was equivalent to that induced by palmitoylated DT-MUC1+αGalCer (P1-DT-MUC1+αGalCer) and significantly higher than that induced by doubly palmitoylated DT-MUC1+αGalCer (P2-DT-MUC1+αGalCer), suggesting that the easily synthesized DT-MUC1 may not require lipid chain modification and already possess good amphiphilicity. This is the first time that a diphtheria toxin-derived helper T-helper epitope was covalently linked to a glycopeptide antigen to enhance its immunogenicity, and this study may provide an effective vaccine design strategy for MUC1-targeted antitumor vaccines and offer novel insights into the design of fully synthetic peptide vaccines.
研究领域:
免疫学
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肿瘤学
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疫苗开发
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DOI
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Qingshuang Zou,Ke Liao,Guangchao Li,Xin Huang,Yongwei Zheng,Gun Yang,Min Luo,Evelyn Y. Xue,Chuanqing Lan,Shuai Wang,Yao Shen,Dixian Luo,Dennis K. P. Ng,Quan Liu
The infiltration and cytotoxicity of chimeric antigen receptor (CAR)-T cells are crucial for effective elimination of solid tumors. While metallo-immunotherapy is a promising strategy that can activate the antitumor immunity, its role in promoting CAR-T cell therapy remains elusive. The first single-element nanomaterial based on chromium nanoparticles (Cr NPs) for cancer photo-metallo-immunotherapy has been reported previously. Herein, an extended study using biodegradable polydopamine as a versatile carrier for these nanoparticles, enabling synergistic CAR-T cell therapy, is reported. The results show that these nanocomposites with or without further encapsulation of the anticancer drug alpelisib can promote the CAR-T cell migration and antitumor effect. Upon irradiation with near-infrared light, they caused mild hyperthermia that can “warm” the “cold” tumor microenvironment (TME). The administration of B7-H3 CAR-T cells to NOD severe combined immunodeficiency gamma mice bearing a human hepatoma or PIK3CA-mutated breast tumor can significantly inhibit the tumor growth after the induction of tumor hyperthermia by the nanocomposites and promote the secretion of serum cytokines, including IL-2, IFN-γ, and TNF-α. The trivalent Cr 3+ ions, which are the major degradation product of these nanocomposites, can increase the CXCL13 and CCL3 chemokine expressions to generate tertiary lymphoid structures (TLSs) in the tumor tissues, facilitating the CAR-T cell infiltration.
研究领域:
肿瘤学
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免疫疗法
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纳米技术
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生物医学工程
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Energy Chemistry
·
2022
·
IF 13.599
Xiaobo Ding,Huiying Huang,Qianhui Huang,Benrui Hu,Xiaokang Li,Xiangdong Ma,Xunhui Xiong
Heteroatoms doping has been regarded as a promising route to modulate the physiochemical properties of electrode materials, in which the doping sites greatly influence the electrochemical performances. However, very few reports focus on enhancing the lithium storage performances of Nb 2 O 5 via heteroatoms doping, yet the effect of different doping sites remains unclear. Herein, nitrogen doping has been proposed to improve the fast-charging capability of orthorhombic Nb 2 O 5 (T-Nb 2 O 5 ) via a urea-assisted annealing process . Experimental data and theoretical calculation demonstrate that the N doping sites in T-Nb 2 O 5 can be tuned by the heating rate , in which substitutional N can increase the spacing of the Li + transport layer as well as reduce the band gap, while interstitial N can provide an electron-rich environment for Li + transport layer and then reduce the Li + diffusion barrier . Arising from the synergistic effect of N doping at different sites, the N-doped T-Nb 2 O 5 without carbon coating delivers impressive rate performance (104.6 mA h g −1 at 25 C) as well as enhanced cycle stability with a retention of 70.5% over 1000 cycles at 5 C. In addition, the assembled lithium ion capacitor exhibits a high energy density of 46.6 Wh kg −1 even at high power density of 8.4 kW kg −1 .
研究领域:
材料科学
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电化学
·
能源存储
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Tiantian An,Zhaoyu Xu,Yang Yang,Xinhui Li,Shuaidong Chen,Xingmei Yang,Yi Man,Chen Hu,Yili Qu
This study investigates the role of γδ T cells in wound healing facilitated by an EGCG (Epigallocatechin gallate)-releasing nanofibrous scaffold with aligned topography (APEMS). Incorporating core-shell microcapsules for sustained EGCG release over 11 days, the biocompatible scaffold enhances γδ T cell activity to promote advanced wound repair. In a splinted wound excisional model in 6-8 weeks-old male C57BL/6J mice, APEMS significantly improved re-epithelialization and wound closure compared to a control scaffold (APS). Single-cell RNA sequencing revealed a marked increase in γδ T cell in the APEMS group, where γδ T cells accounted for 66.2% of the T cell population, compared to 33.8% in the APS group. Cellchat analysis identified the AREG-EGFR signaling axis as pivotal to γδ T cell-mediated wound repair. APEMS-induced γδ T cells secreted amphiregulin (AREG), which acted on keratinocytes and fibroblasts to enhance keratinocyte proliferation, migration, and fibroblast-driven extracellular matrix remodeling. In immunodeficient mice lacking mature γδ T cells (TCRδ-/-), wound healing was significantly impaired, characterized by delayed re-epithelialization, reduced neo-dermal thickness, and increased inflammation. Inhibition of AREG and EGFR function via monoclonal antibodies against AREG and EGFR antagonist Gefitinib similarly delayed wound healing, the therapeutic advantage of APEMS over APS was abolished, emphasizing its critical role in the process. These findings provide a framework for developing advanced wound management materials and highlight the therapeutic potential of targeting γδ T cells and AREG-EGFR signaling to enhance tissue regeneration.
研究领域:
生物材料
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免疫学
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组织工程
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再生医学
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药学
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细胞生物学
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皮肤科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Feng Lin,Hong Huang,Jie Long,Renchuan Liang,Yunxi Huang,Xiaoling Luo
Cancer remains a major global health burden due to its high rates of recurrence and resistance to conventional therapies. Although PD-L1/PD-1 immune checkpoint inhibitors (ICIs) have emerged as promising treatments by restoring T cell function and enhancing anti-tumor immunity, their efficacy is often limited by immunosuppressive tumor microenvironment (ITM) and metabolic adaptations that impair T cell activity. To address these challenges, we developed a novel intelligent drug delivery platform that integrates PANoptosis induction, metabolic modulation and targeted nanotherapy. Specifically, hollow mesoporous manganese dioxide (H-MnO 2 ) nanoshells were synthesized and co-loaded with SOAT1 inhibitor avasimibe (Ava). Trop2-specific targeting ligands were further conjugated to enable precise tumor localization, resulting in the multifunctional nanoplatform Ava@HM/Trop2. Upon tumor accumulation via Trop2-mediated targeting, acidic pH conditions and TME stimuli trigger rapid degradation of the H-MnO 2 nanoshells, releasing Ava and inducing PANoptosis. This process activates the cGAS-STING pathway, remodels immunosuppressive TME, mitigates lipid-induced T cell senescence, and synergizes with PD-1 blockade to potentiate anti-tumor immunity. Both in vitro and in vivo experiments demonstrate that Ava@HM/Trop2 achieves efficient tumor targeting, robust tumor cell apoptosis, and improved therapeutic outcomes. This innovative multi-modal strategy highlights a promising avenue for overcoming immunotherapy resistance and advancing the clinical management of solid tumors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
·
2019
·Vol. 25
·期 67
·15401-15410
·
IF 5.16
Gaowei Qian,Xiangbing Wang,Shengyue Wang,Yanqiong Zheng,Song Wang,Weiguo Zhu,Yafei Wang
Graphical Four ′T′-shaped molecules bearing the 2,1,3-benzothiadiazole skeleton were prepared and characterized. All compounds exhibited excellent thermal stability and polymorphism in the solid state. The structure–property relationship of these compounds was systematically explored. A highest external quantum efficiency of 6.15 %, beyond the theoretical value of fluorescence-based OLEDs (∼5 %), were achieved for the solution-processable OLEDs. Polymorphism, the intrinsic character of one chemical compound with at least two distinct phase arrangements, plays a very key role in the photophysical properties. In this contribution, four ′T′-shaped molecules bearing the 2,1,3-benzothiadiazole (BTD) skeleton, named 5 a – 5 d , were prepared and characterized. All compounds exhibited excellent thermal stability and polymorphism in the solid state, evident from thermogravimetric analysis, differential scanning calorimetry, and polarized optical microscopy results. Intense emissions with high photoluminescent quantum yields were achieved both in solution (56–97 %) and neat films (33–98 %). All compounds possessed clearly pH-dependent luminescence properties in solution. Additionally, compound 5 d showed useful mechanochromic luminescence owing to the transformation between the crystal and amorphous state. Employing compounds 5 a – 5 d as the dopant, solution-processable organic light-emitting diodes (OLEDs) were fabricated and presented a highest external quantum efficiency of 6.15 %, which is higher than the theoretical value of fluorescence-based OLEDs (∼5 %). This research provided a novel strategy for designing high-efficiency BTD-based polymorphic luminescent materials.
研究领域:
材料科学
·
光学
·
有机电子学
✓ 已验证
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yu Han,Kai Zhang,Ning Xin,Xintao Gao,Guohua Ma,Jingtong An,Yantao Li
Despite recent advancements in lipid nanoparticles (LNPs)-based messenger RNA (mRNA) delivery, significant challenges persist in the structural optimization and functional modulation of their components for cancer immunotherapy, particularly regarding inadequate organ-specific targeting, and insufficient immune activation. Notably, metal ions have demonstrated emerging immunomodulatory potential, yet their coordinated self-assembly within LNPs as adjuvants to enhance the immunotherapeutic efficacy remains largely unexplored. To address these limitations, we combine newly designed imidazole-based LNPs with functional metal ions (Zn 2+ ) to develop novel Zn-coordinated LNP-based mRNA vaccines. A total of 48 imidazole-based ionizable lipids were designed and synthesized, among which C2–13 LNPs emerged as the top-performing formulation in terms of transfection efficiency. By innovatively incorporating Zn 2+ into C2–13 LNPs via coordination interaction, we further developed the novel metal-coordinated mRNA delivery systems, referred to as Zn-C2–13 LNPs. Compared to their non-metal counterparts, Zn-C2–13 LNPs exhibited markedly improved transfection efficiency and antigen presentation in vitro . Impressively, the synergistic effect of the optimized LNP formulation and Zn 2+ in the Zn-C2–13/mOVA systems (Zn-C2–13 LNPs loading ovalbumin mRNA) resulted in superior spleen-selective expression and immune response, significantly boosting the efficacy of cancer immunotherapy in the B16F10 ovalbumin-expressing (B16F10-OVA) melanoma tumor model. Collectively, this novel metal-coordinated LNPs improve specific organ targeting and immune responses, presenting a promising strategy to advance mRNA vaccine-based cancer immunotherapy.
研究领域:
免疫学
·
肿瘤学
·
纳米医学
·
分子生物学
·
转化医学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Bin Wang,Maoping Tang,Qijing Chen,William Ho,Yilong Teng,Xiaojian Xiong,Zhitong Jia,Xiuling Li,Xiaoyang Xu,Xue-Qing Zhang
T cell exhaustion has emerged as a major hurdle that impedes the clinical translation of stimulator of interferon genes (STING) agonists. It is crucial to explore innovative strategies to rejuvenate exhausted T cells and potentiate the antitumor efficacy. Here, we propose an approach utilizing MSA-2 as a STING agonist, along with nanoparticle-mediated delivery of mRNA encoding interleukin-12 (IL-12) to restore the function of T cells. We developed a lipid nanoparticle (DMT7-IL12 LNP) that encapsulated IL12 mRNA. Our findings convincingly demonstrated that the combination of MSA-2 and DMT7-IL12 LNP can effectively reverse the exhausted T cell phenotype, as evidenced by the enhanced secretion of cytokines, such as tumor necrosis factor alpha, interferon gamma, and Granzyme B, coupled with reduced levels of inhibitory molecules such as T cell immunoglobulin and mucin domain-3 and programmed cell death protein-1 on CD8+ T cells. Furthermore, this approach led to improved survival and tumor regression without causing any systemic toxicity in melanoma and lung metastasis models. These findings suggest that mRNA encoding IL-12 in conjunction with STING agonists has the potential to confer superior clinical outcomes, representing a promising advancement in cancer immunotherapy.
研究领域:
癌症研究
·
免疫学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Simei Yue,Lingjiao Gong,Yulin Tan,Xiaodan Zhang,Fei Liao
Background Abnormal immune homeostasis, which leads to the accumulation of reactive oxygen species (ROS) and an inflammatory response, plays a crucial role in accelerating the progression of inflammatory bowel disease (IBD). The lack of targeted therapeutic strategies significantly hampers the efficacy of clinical treatments for IBD. This study presents cerium oxide nanoparticle-loaded regulatory T cell-derived exosomes (exo@nCeO) as innovative anti-inflammatory and antioxidant agents specifically designed to address the effects of immune dysregulation.Methods In this work, the morphology and antioxidant properties of nano-cerium oxide were characterized using transmission electron microscopy, as well as hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl radical assays. Tumor necrosis factor-α and dextran sulfate sodium were employed to establish cellular and animal models of IBD. The impact of exo@nCeO on ROS scavenging and anti-inflammatory activity in intestinal epithelial cells was assessed using dihydroethidium and 2,7-dichlorodihydrofluorescein staining, Western blotting, and apoptosis flow cytometry analysis. Hematoxylin and eosin staining, along with immunohistochemistry and immunofluorescence staining, were utilized to evaluate intestinal epithelial inflammation and ROS levels in the IBD mouse model.Results The findings demonstrate that exo@nCeO possesses augmented anti-inflammatory properties and ROS scavenging abilities in intestinal epithelial cells. In murine models of IBD, exo@nCeO effectively maintained the integrity of the intestinal epithelial barrier and impeded the progression of IBD.Conclusion This study introduces a novel therapeutic approach for IBD and underscores a potential strategy for addressing diseases associated with inflammation and oxidative stress.
研究领域:
免疫学
·
纳米医学
·
消化系统疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Oncology
·
2022
·
IF 4.501
Liping Qian,Lihua Mao,Weixing Mo,Rong Wang,Yunlong Zhang
Glioblastoma (GBM) is the most common intracranial tumor with characteristic of malignancy. Resveratrol, a natural originated polyphenolic compound, has been reported to act as a potential radiosensitizer in cancer therapy. Magnetic resonance imaging (MRI) is the first choice for the diagnosis, pathological grading, and efficacy evaluation of GBM. In this study, MRI was applied to observe whether resveratrol could intensify the anti-GBM tumor effect by enhancing antitumor immunity during radiotherapy. We established an intracranial C6 GBM model in SD rats, treated with radiation and resveratrol. The increased body weight, the inhibition on mortality, and tumor volume in radiated- GBM rats were further enhanced by resveratrol addition, while the pathological damage of brain was alleviated. The modulation of radiation on inflammation, cell cycle, and apoptosis was strengthened by resveratrol; and Ki-67, PD-L1, and cell cycle- and apoptosis-related protein expressions were also improved by cotreatment. Besides, cotreatment attenuated DNA damage and induced G0/G1-phase cell arrest of GBM rats, accompanied with the changed expression of ATM-AKT-STAT3 pathway-related proteins. Moreover, the percentages of CD3+CD8+T cells and IFN-γ+CD8+T cells were enhanced, while (CD4+CD25+Foxp3)/CD4+T cells were decreased by radiation or resveratrol, which was strengthened by cotreatment. The modulation effect of cotreatment on CD3, Foxp3, and IFN-γ levels was also stronger than radiation or resveratrol alone. To conclude, resveratrol enhanced the effect of radiotherapy by inducing DNA damage and antitumor immunity in the intracranial C6 GBM.
研究领域:
肿瘤学
·
放射学
·
免疫学
·
神经科学
·
药理学
✓ 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）