Food Bioscience
·
2025
·
IF 5.9
Yixuan Wang,Songyu Yang,Shengbin Chen,Yingbing Zuo,Xiaoyu Mu,Hongmei Zhou,Yufei Yao,Xiaoping Peng,Wenjuan Li
This study aimed to explore the anti-tumor activity and mechanisms of the ethanol-soluble acidic components (ESAC) of Camellia oleifera cake through a combination of network pharmacology, in vitro and in vivo studies, and metabolomics based on UPLC-Q-TOF/MS. Additionally, the potential application of ESAC in combination with PD-1 inhibitors was explored. In this work, our results demonstrated that ESAC exhibited anti-tumor activities mediated by regulated cell death (RCD), which were associated with apoptosis, pyroptosis, and ferroptosis. UPLC-Q-TOF/MS-based serum metabolomics revealed that metabolic disorders were occurred in tumor group when compared to control group. In contrast, ESAC significantly inhibited abnormal energy metabolism including glycolysis, tricarboxylic acid cycle, and amino acid metabolism. Consequently, hexokinase and malate dehydrogenase, key enzymes of energy metabolism, were determined, and data showed that treatment of tumor mice with ESAC significantly suppressed activities of these metabolic enzymes when compared to tumor group, confirming that mitigating metabolic disorders contributed to the anti-tumor activities of ESAC. Moreover, ESAC could also reduced PD-L1 expression in tumor tissue, which was similar to the effect of PD-1 inhibitor. Furthermore, combination treatment with ESAC and PD-1 inhibitor was superior to either treatment alone, and it enhanced pyroptosis through the NLRP3/Caspase-1/GSDMD pathway. Together, we concluded that metabolic correction and PD-L1 inhibition were the critical mechanisms to exert anti-tumor activities of ESAC.
研究领域:
药理学
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肿瘤学
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代谢组学
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产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Wang Haoyue,Sun Kexiang,Tan Wei Shan,Gao Jiamin,Yuan Luyun,Wen Junkai,Deng Wanli
Background A controlled type of cell death called ferroptosis is linked to increased reactive oxygen species (ROS), lipid peroxidation, and iron buildup. Furthermore, evidence indicates that ferroptosis may act as an immunogenic form of cell death with potential physiological functions in tumors and immunosuppression. Inducing ferroptosis in tumor cells may have the potential to complement cancer immunotherapy strategies. The development of colorectal cancer (CRC) and the poor efficacy of immunotherapy are associated with the crosstalk of cellular ferroptosis. Currently, Icariin (ICA), the main bioactive component extracted from Epimedium , has been shown to inhibit a variety of cancers. However, the specific role and potential mechanism of ICA in regulating ferroptosis in CRC remains unclear. Purpose The aim of this investigation was to clarify the mechanism underlying the anti-CRC cancer properties of ICA and how it induces ferroptosis to enhance immunotherapy. Methods To evaluate cell viability, the Cell Counting Kit-8 (CCK-8) test was utilized. The transwell test and the wound healing assay were used to assess cell migration. A subcutaneous graft tumor model was constructed with C57BL/6 mice using MC38 colorectal cancer cell lines. The inhibitory effect of ICA on CRC, ferroptosis level and immunomodulatory effects were detected by serum biochemical assay, cytokine assay, hematoxylin-eosin (H&E) staining, immunofluorescence staining, CyTOF mass spectrometry flow screening and Western blotting. Western blotting, proteomics, molecular docking and microscale thermophoresis (MST) were used to forecast and confirm ICA's binding and interaction with HMGA2, STAT3, and HIF-1α. Moreover, the levels of lipid peroxidation and ferroptosis were assessed through the use of the C11-BODIPY fluorescent probe, the FerroOrange fluorescent probe, the iron level, the malondialdehyde (MDA) and reduced glutathione (GSH) assay kit, and Western blotting analysis. To assess alterations in mitochondrial structure and membrane potential, transmission electron microscopy (TEM) and JC-1 immunofluorescence were employed. Results It was demonstrated in the current study that ICA treatment inhibits CRC and enhances anti-PD-1 therapy efficacy by inciting ferroptosis. As shown in vitro, ICA inhibits CRC cell proliferation, migration, and apoptosis. As demonstrated in vivo, ICA has a dose-dependent tumor suppressor effect when combined with anti-PD-1, it can significantly inhibit tumor growth, increase the expression of serum TNF-α, IFN-γ, and granzyme B, and promote CD69 + CD8 + T, CD69 + CD8 + Tem, CD69 + CD8 + Teff, TCRβ + CD8 + T, TCRβ + CD8 + T, TCRβ + CD8 + Tem, TCRβ + CD8 + Teff. The inhibitory effect of ICA on CRC was associated with the binding of HMGA2, STAT3, and HIF-1α proteins, which inhibited CRC by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), promoting the accumulation of iron (Fe 2+ ), depletion of reduced glutathione (GSH), inhibiting SLC7A11 and GPX4 expressions, thereby inducing ferroptosis in CRC. As a consequence of ICA-induced ferroptosis, mitochondria are dysfunctional, with increased ROS production, membrane potential depolarization (MMP), and ATP production reduced. This process can be efficiently reversed by the mitochondria-targeted antioxidant Mito-Q. It is noteworthy that the ferroptosis inhibitor liproxstatin-1 (lip-1), anti-CD8, and anti-IFN-γ exhibited a significant inhibitory effect on the level of ferroptosis and antitumor capacity of ICA combined with anti-PD-1. This finding suggests that the antitumor immunopotentiating effect of ICA on anti-PD-1 is dependent on the secretion of IFN-γ-induced ferroptosis of CRC cells by the CD8 + T cell. Conclusion Our study represents the inaugural demonstration of the mechanism whereby ICA exerts anti-CRC effects and synergistically enhances the efficacy of anti-PD-1, inducing mitochondrial damage and leading to ferroptosis. ICA promotes ferroptosis of CRC cells by inducing mitochondrial dysfunction, and ICA combined with anti-PD-1 significantly promotes CD69, TCRβ signalling, activates effector CD8 + T cells to secrete IFN-γ, and achieves immunopotentiation by promoting ferroptosis of CRC cells, thus inhibiting CRC development. This study is built upon existing research into the pharmacodynamic mechanisms of ICA in the context of CRC, and offers a novel therapeutic approach in addressing the issue of CRC immunotherapy potentiation.
研究领域:
肿瘤学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Liangyin Wei,Hong Wang,Xietao Ye,Junfan Yue,Hong Guo,Dengxuan Mao,Xia Li,Yeyang Sun,Congyan Liu,Yuping Liu,Yan Chen
The response rate of programmed cell death protein-1 (PD-1) inhibitors in breast cancer remains unsatisfactory, primarily due to the limited infiltration and activity of tumor-infiltrating T lymphocytes (TILs). Previous studies demonstrated that oxymatrine (Om) and astragaloside IV (As) could enhance TIL infiltration and function by inhibiting cancer-associated fibroblasts (CAFs) and promoting mitochondrial activity in TILs, respectively. Thus, combining Om and As may be a promising strategy to improve the antitumor effects of PD-1 inhibitors in breast cancer. However, co-delivery above drugs into breast cancer tissue is challenging due to their low bioavailability and distinct physicochemical properties. This study addresses this challenge by formulating Om and As co-loaded liposomes (Om-As-Lip) and comparing the scale-up production methods: high-pressure homogenization (EP-HPH) and microfluidics. Om-As-Lip prepared via microfluidics demonstrated superior entrapment efficiency (As: 99.03 ± 0.04%, Om: 67.01 ± 0.02%) and a significantly higher production rate (22.12 mL/min) compared to EP-HPH (1.19 mL/min). Additionally, Om-As-Lip produced by microfluidics increased the area under the curve (AUC) (Om: 6.17-fold, As: 2.07-fold) and maximum concentration (Cmax) (Om: 1.58-fold, As: 3.49-fold) compared to the free drugs. Importantly, Om-As-Lip enhanced the antitumor efficacy of α-PD-1 by inhibiting CAF activation and boosting TIL activity, resulting in a tumor inhibition rate of 61.2% and extended survival in mice. This work presents a novel perspective for scaling up co-delivered formulations of drugs with differing polarities to improve breast cancer immunotherapy.
研究领域:
药学
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肿瘤免疫学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
BMC MICROBIOLOGY
·
2024
·Vol. 24
·期 1
·1-15
·
IF 4
Wang Benlin,Qiu Yifeng,Xie Ming,Huang Pengcheng,Yu Yao,Sun Qi,Shangguan Wentai,Li Weijia,Zhu Zhangrui,Xue Jingwen,Feng Zhengyuan,Zhu Yuexuan,Yang Qishen,Wu Peng
Objective Bladder cancer(BCa) was a disease that seriously affects patients’ quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. Methods We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. Results The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4 + T and CD8 + T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. Conclusion P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.
研究领域:
肿瘤学
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微生物学
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免疫学
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分子生物学
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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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.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Mengdan Shen,Xi Han,Xixi Li,Jiayun Ji,Shunyao Zhu,Beihua Xu,Senlin Shi,Ting Zhang
In this study, emodin (ED) and polysialic acid (PSA) were synthesized into a compound called PSA-ED. The PSA-ED self-assembled into nanoparticles (PE-NS) using a nano-precipitation method. According to the results of particle size analyzer, the particle size of PE-NS was 180.7 ± 1.60 nm, the polydispersity index (PDI) was 0.263 ± 0.090, and the ζ potential was −17.1 ± 0.9 mV. In vitro cellular experiments confirmed that compared to free emodin, PE-NS exhibited significantly higher cellular uptake in RAW264.7 cells. In addition, in vivo imaging demonstrated enhanced fluorescence accumulation in tumors. This indicated that PE-NS possesses the ability to effectively target tumor-associated macrophages (TAMs). We conducted experiments using a mouse model of the B16F10 tumor, treating the mice with PD-1 antibody, PE-NS, and various doses of PE-NS + anti-PD-1 antibody, and compared them with untreated controls. In the PE-NS and anti-PD-1 antibody combination therapy group, there was a notable decrease in the proportion of M2-TAMs and CD4 + Fop3+ T cells, alongside a significant increase in the proportion of M1-TAMs and CD8+ T cells, resulting in an increased tumor inhibition rate. The combination of PE-NS and anti-PD-1 antibody exhibited synergistic antitumor activity, enhancing the effectiveness of PD-1 checkpoint blockers in the mouse melanoma models. In conclusion, the combination of PE-NS and anti-PD-1 antibody immunotherapy holds great promise in improving the therapeutic effects of melanoma treatment and may offer a novel strategy for clinical application.
研究领域:
纳米技术
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免疫学
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肿瘤学
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Qi Chen,Yue Zhou,Xudong Zhu,Lei Xu,Ge Bai,Yaru Zhou,Nannan Zhang,Hongwen Liu,Yani Pan,Yu Liu,Lishan Wang,Xueni Fu,Jingjing Wei,Lina Zhou,Lu Xu,Yuxiang Sun,Zhangding Wang,Shanshan Shen,Yun Zhu,Lei Wang
Tumor-associated neutrophils (TANs), particularly the N2 phenotype, contribute to T cell exhaustion in cholangiocarcinoma (CCA), leading to low response rates to PD-1 inhibitor therapy. To address this issue, cancer-associated fibroblast (CAF)-derived extracellular vesicles loaded with ruxolitinib (CEVs@Ru) are developed to selectively target and reprogram N2 TANs, thereby modulating the immunosuppressive tumor microenvironment (TME). The combination of CEVs@Ru with anti-PD-1 antibody therapy significantly enhanced antitumor efficacy, reducing tumor weight by 89.86% and normalizing liver weight, without significant adverse effects. This approach improved the local concentration of ruxolitinib, increased CD8+ T cell infiltration, and reduced regulatory T cells, indicating a remodeled TME conducive to effective antitumor immunity. The findings provide a promising strategy for enhancing PD-1 inhibitor efficacy and improving patient outcomes in CCA and potentially other solid tumors.
研究领域:
肿瘤学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-15
·
IF 12.6
Wang Xingyi,Fang Hanyi,Hu Wenzhu,Feng Yuan,Zhou Zhangyongxue,Hu Mengyan,Jiang Dawei,Zhang Yongxue,Lan Xiaoli
Limited treatment response and inadequate monitoring methods stand firmly before successful immunotherapy. Recruiting and activating immune cells in the hypoxic tumor microenvironment is the key to reversing immune suppression and improving immunotherapy efficacy. In this study, biomimetic oxygen-delivering nanoparticles (CmPF) are engineered for homologous targeting and hypoxia alleviation within the tumor environment. CmPF targets the tumor microenvironment and delivers oxygen to reduce hypoxia, thereby promoting immune cell activity at the tumor site. In addition, granzyme B-targeted positron emission tomography (PET) imaging is employed to monitor immune cell activity changes in response to immunotherapy efficacy in vivo. The combination of CmPF with carboplatin and PD-1 inhibitors significantly suppresses tumor growth by 2.4-fold, exhibiting the potential of CmPF to enhance the efficacy of immunotherapy. Immunohistochemistry further confirms increased expression of key immune markers, highlighting the reprogramming of the tumor microenvironment. This study demonstrates that hypoxia alleviation enhances tumor immunotherapy efficacy and introduces a non-invasive PET imaging method for dynamic, real-time assessment of therapeutic response.
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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医学影像
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Feng-Yang Wang,Liang-Mei Yang,Xiao-Lin Xiong,Jing Yang,Yan Yang,Jiu-Qin Tang,Lei Gao,Yuan Lu,Yuan Wang,Taotao Zou,Hong Liang,Ke-Bin Huang
Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/β-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in β-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.
研究领域:
肿瘤学
·
免疫学
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化学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Guo Hong,Li Xia,Mao Dengxuan,Wang Hong,Wei Liangyin,Qu Ding,Qin Xiaoying,Li Xiaoqi,Liu Yuping,Chen Yan
The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone II A (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal–organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Wei Duan,Rendy Hosea,Lingxian Wang,Cao Ruan,Fuqiang Zhao,Jingyi Liu,Hezhao Zhao,Makoto Miyagishi,Shourong Wu,Vivi Kasim
Immune checkpoint inhibitor (ICI) therapy is a promising anti-tumor therapeutic strategy; however, its efficacy in solid tumors is limited. Chromosome missegregation is common in various solid tumors; however, its role in tumor progression remains poorly understood, and its correlation with ICI is yet to be explored. Here, it is found that increased chromosome missegregation promotes tumor immune microenvironment, and eventually immunotherapeutic efficacy, by triggering pyroptosis. yin yang 2 (YY2) is identified as a mitotic checkpoint regulator, which promotes chromosome missegregation by upregulating BUB1B transcription. Increased chromosome missegregation promoted the formation of micronuclei and release of double-stranded DNA (dsDNA) into the cytosol, triggering an AIM2-mediated cytosolic dsDNA response. The subsequent pyroptosis strengthened the tumor immune microenvironment, thereby enhancing immunoinfiltration and cytotoxicity of CD8 + T cells, while preventing their exhaustion. Finally, through in vitro and in vivo experiments, it is demonstrated that combining YY2 overexpression-induced chromosome missegregation/cytosolic dsDNA response and PD-1 inhibitor significantly enhanced the efficacy of ICI immunotherapy in microsatellite instable and microsatellite stable colorectal cancer cells. Together, these findings provide new insights on the role of chromosome missegregation in triggering cytosolic dsDNA response-mediated pyroptosis and modulating the tumor immune microenvironment, suggesting a novel strategy for improving ICI therapeutic efficacy in colorectal cancer.
研究领域:
肿瘤学
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免疫学
·
分子生物学
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2024
·
IF 4.3
Shaofei Yuan,Linjia Zhu,Yi Luo,Xiaoqiang Chen,Haibo Jing,Jiaqi Wang,Xiangyu Su,Meizhen Liang,Zhixiang Zhuang
Eliciting tumour microenvironment (TME) activation in triple-negative breast cancer (TNBC) is crucial for effective anti-tumour therapies. The aim of this study is to employ pharmaceutical approaches to precisely deliver Ganoderma polysaccharide (GPS) to tumour sites, thereby enhancing TME activation. We first established a direct link between the accumulation of GPS within tumours and its efficacy in the TME activation. Building upon this insight, we then engineered a mannose/hyaluronic acid dual-coated GPS-loaded superparamagnetic iron oxide nanocomplex (Man/HA/GPS-SPIONs) with a particle size of 33.8 ± 1.6 nm and a zeta potential of −22.4 ± 3.5 mV, capable of precise tumour accumulation through magnet-assisted targeting and internalisation by tumour-associated macrophages (TAMs) and tumour cells, facilitated by dual ligand modification. In vitro, Man/HA/GPS-SPIONs effectively induced M1 polarisation of macrophages (CD86+ cells: 38.6 ± 2.8%), curbed 4T1 cell proliferation (viability: 47.3 ± 2.9%) and heightened Th1 cytokine release. Significantly, in vivo, Man/HA/GPS-SPIONs notably suppressed tumour growth (tumour index: 0.048 ± 0.005), fostered M1 polarisation of TAMs (CD45+F4/80+CD86+ cells: 26.1 ± 7.2%), consequently bolstering intratumoural T cytotoxic cells. This enhancement was intricately tied to the efficient co-delivery of GPS and iron ions to the tumours, made possible by the Man/HA/GPS-SPIONs delivery system. The synergistic effects with paclitaxel (PTX, inhibition rate: 61.2 ± 4.3%) and PD-1 inhibitors (inhibition rate: 69.8 ± 7.6%) underscored the translational potential of this approach. By harnessing a well-conceived iron-based drug delivery strategy, this study amplifies the tumour immune modulatory potential of natural polysaccharides, offering insightful guidance for interventions in the TME and synergistic therapies.
研究领域:
肿瘤学
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药学
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纳米技术
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免疫治疗
✓ 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）