Journal of Inflammation Research
·
2025
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IF 4.1
Shiwen Zhang,Changqiang Wang,Jing Jiang,Linlu Li,Jiaqi Luo,Jingying Zhu,Renxu Chen
Background Immune escape of tumor cells is a common problem with tumor photothermal therapy utilizing gold nanorods (Au NRs). Whether CpG ODN, an immune adjuvant, can synergize with Au NRs to activate the immune response and its potential mechanism is not clear.Methods The effect of Au NRs combined with CpG ODN (Au NRs-C) on the activity of various immune-related cells, such as double-positive T cells, macrophages, NK cells, Th17, and Treg. The expression levels of various immune and inflammation-related factors, such as IL-1R1, IL-6, IL-17, and TNF-α were characterized. Transcriptome sequencing analysis was used to explore the potential immunomodulatory mechanisms of Au NRs-C. Whether immune activation was enhanced by antibody-functionalized Au NR upon binding to CpG ODN was assessed.Results Flow cytometry and ELISA analyses indicate that both Au NRs and CpG ODN increase pro-inflammatory cytokine levels and immune activation. However, Au NRs-C demonstrated superior immune activation potential. Furthermore, Au NRs stimulate the expression of Treg, while Au NRs-C significantly inhibit this effect. This suggests that the conjugation of CpG ODN with Au NRs not only greatly enhances the immune activation but also compensates for some of their deficiencies in eliciting immune responses. Transcriptome sequencing uncovered DEGs mainly localized to immune and pro-inflammatory cytokine pathways. PPI analysis identified six hub genes: FOXM1, HMOX1, UBE2C, E2F1, PECAM1, and FCGR3A. Moreover, CpG conjugation with antibody functionalization- Au NRs enhances immune stimulation.Conclusion Au NRs-C promotes immune activation by eliciting changes in the activity of immune-associated cells and expression of inflammatory factors through multiple pathways, such as MHC antigen presentation and Toll-like receptor-mediated immune processes.
研究领域:
免疫学
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纳米医学
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癌症生物学
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生物信息学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 31
·4854-4866
·
IF 5.047
Xuanjin Wu,Yang Li,Xiguang Chen,Zhongzheng Zhou,Jianhui Pang,Xin Luo,Ming Kong
The efficient delivery of vaccines to draining lymph nodes and the induction of robust local immune responses are crucial for immunotherapy. Transdermal administration has been evidenced to facilitate the delivery of ingredients to lymph nodes. In this study, transfersomes with opposite surface charges were applied for antigen encapsulation and these were integrated with dissolving microneedles to investigate their effects on immune responses via transdermal immunization. The microneedles were easily inserted into mouse skin and achieved the local release of nanovaccines into the dermis through dissolution. Although anionic nanovaccines promoted cellular uptake via DC2.4, cationic nanovaccines exhibited stronger escape capacities from endocytic compartments, facilitating antigen processing via an MHC-I presentation pathway, and formed larger accumulations in lymph nodes. Compared with their anionic counterparts, the cationic nanovaccines more efficiently activated DC maturation and induced Th1 immunity; this was suggested by the significantly increased IgG2a/IgG1 ratio and elevated cytokine secretion from Th1 cells, without an enhancement in the Th2 response. Such an enhanced Th1 antigen-specific immune response in lymph nodes via a transdermal vaccine delivery platform is beneficial for potential immunotherapy approaches.
研究领域:
免疫学
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药学
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纳米技术
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疫苗递送系统
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Dandan Jiang,Weiwei Mu,Xiuping Pang,Yongjun Liu,Na Zhang,Yunmei Song,Sanjay Garg
Enhancing cytosol delivery of exogenous antigens in antigen presenting cells can improve cross-presentation and CD8+ T cell-mediated immune response. The antigen cytosol delivery speed, which has great importance on the rate of MHC class I molecules (MHC I) antigen presentation pathway and cytotoxic T lymphocytes (CTLs) induction, has not been well studied. We hypothesized that micelle-tailored vaccine with multiple cascaded lysosomal responsive capabilities could accelerate lysosomal escape and enhance cancer immunotherapy. To test our hypothesis, we created a novel micellar cancer vaccine (ovalbumin-loaded pH/redox dual-sensitive micellar vaccine, OLM-D) by cleavable conjugation of an antigen with house-made amphiphilic poly(l-histidine)–poly(ethylene glycol) (PLH–PEG) in current study. OLM-D was supposed to achieve cascade cytosol delivery of ovalbumin through three steps in terms of (i) initial redox triggered ovalbumin release, (ii) promoted proton inflow and micelle disassembly, and (iii) speeded proton sponge effect and lysosome bulging/broke. Redox-sensitive antigen release and consequently accelerative OLM-D disassembly were confirmed by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS–PAGE), transmission electronic microscopy (TEM), particle sizes, zeta potentials, and in vitro Ova release evaluation. The speeded cytosol delivery of ovalbumin was visualized under a confocal laser scanning microscope (CLSM). The ability of OLM-D to increase the MHC I molecule combination rate and antigen cross-presentation efficiency was identified by antigen presentation assay and maturation assay in bone marrow-derived dendritic cells (BMDCs). In vivo, the capability of OLM-D to accumulate in draining lymph nodes (LNs) after injection was visualized by real-time near infrared fluorescence imaging (NIRF) and the distribution order in different LNs was first observed (a, d, c, b). Enhanced cancer immunity of OLM-D was confirmed by increased CD3+CD8+ T cell quantity, CD3+CD8+25D11.6+ T cells quantity, and IFN-γ, IL-2 secretion post subcutaneous or intraperitoneal injection (p < 0.05). Taken together, our results indicated that OLM-D provided a promising cascade cytosol delivery strategy, which held great potential to guide further design of nano-particulate cancer vaccines for efficient cancer immunotherapy.
研究领域:
癌症免疫学
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药学
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纳米技术
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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
·
2024
·
IF 18.5
Lei Cao,Dongsheng Tang,Zhen Yu,Yue Shen,Yang Wang,Yue-Qin Li,Juan Chen,Zhao-Qian Liu,Ji-Ye Yin,Haihua Xiao,Xiang-Ping Li
Endogenous T cell activation relies on recognizing tumor-specific antigens. However, tumor cells often alter phenotypes to evade immune surveillance, resulting in immune escape and drug resistance. Photodynamic therapy (PDT) activates anti-tumor immune responses by generating reactive oxygen species, which induce endoplasmic reticulum stress and immunogenic cell death. The clinical application of PDT is limited by immunosuppressive tumor microenvironment. Notably, enhancer of zeste homolog 2 (EZH2) regulates expression of immune-related genes in tumor and immune cells through H3K27 methylation. Consequently, targeting EZH2-mediated epigenetic silence provides an effective strategy to enhance the anti-tumor immune effect of PDT. In this study, a nano-delivery system (NP2) is designed to demonstrate PDT and epigenetic reprogramming effects. NP2 can reverse epigenetic silence, enhance MHC-I expression, and induce release of CXCL9-10 via EZH2i. Meanwhile, NP2 has a significant effect on PDT, inducing endoplasmic reticulum stress that resulted in immunogenic cell death and subsequent activation of the immune cascade. In a mouse model of in situ breast cancer, the combination of PDT activation and epigenetic reprogramming through EZH2i showed synergistic effects on remolding, and triggering a robust anti-tumor immune response in vivo. This study provides a novel idea for improving the immunosuppressive environment in clinical individualized immunotherapy.
研究领域:
癌症生物学
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免疫学
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纳米技术
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Food Science and Human Wellness
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2024
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IF 5.6
Yanan Liu,Huan Li,Chong Wang,Shanjun Chen,Renjie Lian,Weiqiang Wang,Linglin Fu,Yanbo Wang
Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk. However, its influences on immunological components, especially the function of key immune cells, are still poorly known. In this work, we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells, dendritic cells, and T cells. The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine. Moreover, it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells, especially those related to allergy. At the same time, the proportion of MHC class II-positive dendritic cells and the proportion of T helper 2 (Th2) cells in CD4 + T cells increased after histamine stimulation. We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines, disrupt the balance of the immune homeostasis, and potentially lead to adverse immune reactions. This work demonstrated the importance of including the estimation of histamine's immune safety in aquatic products rather than merely considering the potential risk of food poisoning.
研究领域:
免疫学
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食品科学
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毒理学
✓ 已验证
产品关联
DOI
高影响因子
ORAL DISEASES
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2024
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IF 2.9
Qin Jiang,Fang Wang,Gang Zhou
Objective Oral lichen planus (OLP) is a chronic inflammatory disease characterized by a dense T-cell infiltration and the degeneration of basal keratinocytes. The potential functions of mucosal associated invariant T (MAIT) cells in OLP have been analyzed in our previous study. Keratinocytes under proinflammatory conditions have been demonstrated to activate T cells. This study was aimed to investigate how keratinocytes stimulate MAIT cells in OLP, and to explore the role of activated MAIT cells on keratinocytes. Methods and Results Increased MAIT cells and higher activation marker CD69 were detected in OLP lesions by flow cytometry. The enhanced expression of MHC class I-like molecule (MR1) required for MAIT cell activation in the epithelial layer of OLP lesions was determined by immunohistochemistry. Keratinocytes treated by 5-A-RU prodrug and lipopolysaccharide, respectively, exhibited higher expression of MR1 and secretion of IL-18. In direct coculture systems consisting of keratinocytes and peripheral blood mononuclear cells, both 5-A-RU prodrug-pretreated keratinocytes and lipopolysaccharide-pretreated keratinocytes activated MAIT cells to secrete granzyme B, contributing to elevated keratinocyte apoptosis. Conclusions Keratinocytes were capable to activate MAIT cells via MR1 and cytokines in OLP, and granzyme B produced by activated MAIT cells intensified keratinocyte apoptosis, engaging in the pathogenesis of OLP.
研究领域:
免疫学
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皮肤病学
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口腔病理学
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
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IF 26.8
Yinghao Ding,Xueying Zhu,Jian Wen,Junchao Xiong,Shengyi Zhang,Zhimou Yang,Zhi-Wen Hu
Antigen presentation deficiency restricted by class I major histocompatibility complex (MHC-I) causes low antigenicity and antigen escape in tumors, thereby limiting T-cell immunotherapy outcomes. Here, a combined tumor immunotherapy is developed, in which tumors can present exogenous non-tumor antigens, and adoptively transferred CD8 + T cells specific for these antigens are re-targeted to attack tumors. The approach leverages a cascade-responsive peptide self-assembly to co-deliver suitable antigens and the chemotherapeutic drug camptothecin (CPT) to tumors. As a proof-of-concept, to re-target ovalbumin (OVA)-specific OT-I CD8 + T cells against tumors, PSA (Nap-GFFpYE-ss-Ag) and CPSA (CPT-GFFpYE-ss-Ag) are constructed, containing an OVA-derived epitope OVA 257-264 and/or CPT. The design enables the release of a unique N-terminal extended OVA 257-264 and CPT into the cytosol. As a result, the extended antigen is efficiently presented on the tumor surface by MHC-I, and CPT further enhances this presentation. When combined with adoptively transferred OT-I CD8 + T cells, the approach effectively facilitates CD8 + T cell infiltration and tumor inhibition. Additionally, CPSA treatment sensitizes immune responses to programmed cell death-ligand 1 (PD-L1) blockade, allowing the approach to synergize with an anti-PD-L1 antibody for improved tumor eradication.
研究领域:
肿瘤免疫学
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纳米医学
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药物递送系统
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免疫治疗
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分子自组装
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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2022
·
IF 3.511
Wentao Sun,Yang Zhou,Hongmei Xue,Haitao Hou,Guowei He,Qin Yang
Although the association of elevated homocysteine level with cardiac hypertrophy has been reported, the molecular mechanisms by which homocysteine induces cardiac hypertrophy remain inadequately understood. In this study we aim to uncover the roles of cyclic nucleotide phosphodiesterase 1 (PDE1) and endoplasmic reticulum (ER) stress and their relationship to advance the mechanistic understanding of homocysteine-induced cardiac cell hypertrophy. H9c2 cells and primary neonatal rat cardiomyocytes are exposed to homocysteine with or without ER stress inhibitor TUDCA or PDE1-specific inhibitor Lu AF58027, or transfected with siRNAs targeting PDE1 isoforms prior to homocysteine-exposure. Cell surface area is measured and ultrastructure is examined by transmission electron microscopy. Hypertrophic markers, PDE1 isoforms, and ER stress molecules are detected by q-PCR and western blot analysis. Intracellular cGMP and cAMP are measured by ELISA. The results show that homocysteine causes the enlargement of H9c2 cells, increases the expressions of hypertrophic markers β-MHC and ANP, upregulates PDE1A and PDE1C, promotes the expressions of ER stress molecules, and causes ER dilatation and degranulation. TUDCA and Lu AF58027 downregulate β-MHC and ANP, and alleviate cell enlargement. TUDCA decreases PDE1A and PDE1C levels. Silencing of PDE1C inhibits homocysteine-induced hypertrophy, whereas PDE1A knockdown has minor effect. Both cAMP and cGMP are decreased after homocysteine-exposure, while only cAMP is restored by Lu AF58027 and TUDCA. TUDCA and Lu AF58027 also inhibit cell enlargement, downregulate ANP, β-MHC and PDE1C, and enhance cAMP level in homocysteine-exposed primary cardiomyocytes. ER stress mediates homocysteine-induced hypertrophy of cardiac cells via upregulating PDE1C expression Cyclic nucleotide, especially cAMP, is the downstream mediator of the ER stress-PDE1C signaling axis in homocysteine-induced cell hypertrophy.
研究领域:
心脏病学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Xiaodi Li,Pengfei Yuan,Haiyuan Yang,Xiaoqing Zong,Caiqi Yang,Xinjie Chen,Yuchao Li,Xiaodie Yan,Yaoqi Wen,Tianci Zhu,Qian Zhang,Wei Xue,Jian Dai
One of the major causes of immunotherapy resistance is the loss of major histocompatibility complex class I (MHC-I) molecules in tumor cells or the downregulation of the class I antigen presentation pathway. In this study, a novel virus-like nanotherapeutic (siRNA@HCM) is developed via encapsulating nanosized siRNA nanoparticles in a hybrid membrane comprising a personalized tumor cell membrane and a universal 293T membrane expressing the mutant vesicular stomatitis virus glycoprotein (mVSV-G). Upon intravenous administration, siRNA@HCM accumulates at the tumor site and provides two potent driving forces for antitumor immunity. First, mVSV-G induces the fusion of siRNA@HCM with tumor cell membranes and directly injects siRNAs into the cytoplasm, significantly improving tumor intrinsic MHC-I antigen presentation. Moreover, mVSV-G can promote the maturation of dendritic cells, thereby achieving highly efficient antigen cross-presentation. The results demonstrate that spatiotemporally enhancing tumor intrinsic antigen presentation and cross-presentation via siRNA@HCM can achieve satisfactory antitumor efficacy and excellent biocompatibility. Immune infiltration analysis shows that siRNA@HCM treatment turns cold tumors into hot tumors. In addition, it significantly promotes the therapeutic effect of programmed death-1 inhibitor. In summary, virus-like nanotherapeutics present a promising approach to enhance the antitumor immune response, with distinct advantages for potential personalized therapy and clinical applications.
研究领域:
肿瘤学
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免疫学
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纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Liangting Shao,Jingwen Wang,Haijing Hu,Xinglian Xu,Huhu Wang
Microbial spoilage of meat products is a significant problem in the food industry. Aeromonas salmonicida is a significant microorganism responsible for spoilage in chilled meat. Its effector protein, hemagglutinin protease (Hap), has been identified as an effective substance for degrading meat proteins. The ability of Hap to hydrolyze myofibrillar proteins (MPs) in vitro demonstrated that Hap has obvious proteolytic activity, which could alter MPs’ tertiary structure, secondary structure, and sulfhydryl groups. Moreover, Hap could significantly degrade MPs, focusing primarily on myosin heavy chain (MHC) and actin. Active site analysis and molecular docking revealed that the active center of Hap was bound to MPs via hydrophobic interaction and hydrogen bonding. It may preferentially cleave peptide bonds between Gly44-Val45 in actin, and Ala825-Phe826 in MHC. These findings suggest that Hap may be involved in the spoilage mechanism of microorganisms and provide crucial insights into the mechanisms of meat spoilage induced by bacteria.
研究领域:
食品科学
·
微生物学
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蛋白质化学
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结构生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Jiechang Liang,Lei Ding,Zilin Yu,Xingcai Zhang,Shiguo Chen,Yuanfeng Wang
Programmable smart textiles with adaptive moisture/heat conditioning (MHC) capabilities are globally being sought to meet the requirements of comfort, energy efficiency, and health protection. However, a universal strategy for fabricating truly scalable and customizable MHC textiles is lacking. In this study, we introduce a scalable in situ grafting approach for the continuous fabrication of two series of smart textile yarns with opposite thermoresponsive wetting behaviors. In particular, the wetting transition temperature can be precisely programmed by adjusting the grafting formula, making the yarns highly customizable. The smart yarns demonstrated excellent mechanical strength, whiteness, weavability, biocompatibility, and washability (with more than 60 home washes), comparable to those of regular textile yarns. They can serve as building blocks independently or in combination to create smart textiles with adaptive sweat wicking and intelligent moisture/heat regulation capabilities. A proposed hybrid textile integrating both the two series of smart yarns can offer dry-contact and cooling/keep-warming effects of approximately 1.6/2.8 °C, respectively, in response to changes in ambient temperature. Our method provides a rich array of design options for nonpowered MHC textiles while maintaining a balance between traditional wearing conventions and large-scale production.
研究领域:
材料科学
·
纺织工程
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纳米技术
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生物医学工程
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Weihan Zhang,Shijun Yuan,Zipeng Zhang,Shunli Fu,Shujun Liu,Jinhu Liu,Qingping Ma,Zhenxing Xia,Panpan Gu,Shuying Gao,Zhiyue Zhang,Xinke Zhang,Yongjun Liu,Na Zhang
Tumor cells transmit various immunosuppressive signals and induce a dysfunctional state in T cells, which essentially leads to immune escape and tumor progression. However, developing effective strategies to counteract the domestication of T cells by tumor cells remains a challenge. Here, we prepared pH-responsive lipid nanoparticles (NL/PLDs) co-loaded with PCSK9 shRNA, lonidamine (LND), and low-dose doxorubicin (DOX). NL/PLDs can awaken domesticated T cells function by sending pro-activation, pro-recognition, and pro-killing signals by increasing tumor immunogenicity, increasing the expression of major histocompatibility complex I (MHC-I) on tumor cells, and alleviating the suppression effect of tumor-secreted lactic acid (LA) on the T cell effector function, respectively. In melanoma-bearing mice, NL/PLDs effectively relieved tumor immunosuppressive microenvironment (TIME) and enhanced the antitumor immunity mediated by CD8 + T cells. Furthermore, when combined with aPD-1, NL/PLDs demonstrated strong antitumor effects and increased immunotherapeutic efficacy. This regulatory strategy provides new insights for enhancing immunotherapy by regulating tumor immunosuppressive signals and shows significant potential for clinical tumor treatment.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
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）