Journal of Inflammation Research
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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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DOI
PubMed
高影响因子
Theranostics
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2018
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IF 8.537
Chunhui Lai,Siliang Duan,Fang Ye,Xiaoqiong Hou,Xi Li,Jin Zhao,Xia Yu,Zixi Hu,Zhuoran Tang,Fengzhen Mo,Xiaomei Yang,Xiaoling Lu
Purpose: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. Methods: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2 180-188 peptide as liposomal vaccine. M/CpG-ODN-TRP2-Lipo treatment was used to intendedly induce activation of DCs and antitumor- specific immune response in vivo. Results: Our results demonstrated in vitro that the prepared liposomal particles were efficiently taken up by DCs. This uptake led to an enhanced activation of DCs, as measured by the upregulation of MHC II, CD80, and CD86. Furthermore, M/CpG-ODN-TRP2-Lipo effectively inhibited the growth of implanted B16 melanoma and prolonged the survival of mice. This therapy significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, while simultaneously increasing the number of activated T cells, tumor antigen-specific CD8 + cytotoxic T cells, and interferon-γ-producing cells. At the same time, it was found to suppress tumor angiogenesis and tumor cell proliferation, as well as up-regulate their apoptosis. Interestingly, MyD88-knockout mice had significantly shorter median survival times compared to wild-type mice following the administration of M/CpG-ODN-TRP2-Lipo. Conclusions: The results suggested that the antitumor activities of the vaccine partially rely on the Myd88 signaling pathway. Interestingly, compared to whole tumor cell lysate-based vaccine, M/CpG-ODN-TRP2-Lipo, tumor specific antigen peptide-based vaccine, improved survival of tumor-bearing mice as well as enhanced their antitumor responses. All in all, we describe a novel vaccine formulation, M/CpG-ODN-TRP2-Lipo, with the aim of improving antitumor responses by alleviating the immunosuppressive environment in tumors.
研究领域:
免疫学
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肿瘤学
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药学
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生物技术
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DOI
PubMed
高影响因子
PLoS One
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2015
·Vol. 10
·期 10
·e0140265
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IF 3.234
Hengrui Zheng,Songsong Wen,Yang Zhang,Zhenliang Sun
Cytosine–guanine (CpG) containing oligodeoxynucleotides (ODN) have significant clinical potential as immunotherapeutics. However, limitations exist due to their transient biological stability in vivo , lack of specificity for target cells, and poor cellular uptake. To address these issues, we prepared amine magnetic mesoporous silica nanoparticles (M-MSN-A) then further modified with polyethylene glycol (PEG) for use as CpG delivery vectors. The PEG modified M-MSN-A (M-MSN-P) had notable CpG ODN loading capacity, negligible cytotoxicity, and were easily internalized into cells where they released the loaded CpG into the cytoplasm. As a result, such complexes were effective in activating macrophages and inhibiting tumor cells when combined with chemotherapeutics in vitro . Furthermore, these complexes had excellent immuno-stimulating activity in vivo , compared to the free CpG therapeutics. We report here a highly effective MSNs-based delivery system with great potential as a therapeutic CpG formulation in cancer immunotherapy.
研究领域:
生物材料学
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免疫学
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肿瘤学
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DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
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2026
·Vol. 83
·期 1
·76
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IF 6.2
Feiyu Lu,Shengnan Wang,Mengru Zhu,Kuo Qu,Tong Zhu,Hong Wang,Yongli Yu,Liying Wang
The imbalanced expression of interferon regulatory factor (IRF) 4 and IRF8 in activated B cells significantly influences their differentiation and promotes the development of immune-related diseases. Restoring abnormal B cells to appropriate responses may treat these diseases. In this study, an oligodeoxynucleotide (ODN) S2, designed according to the consensus sequence recognized by IRFs in interferon-stimulated response elements, was used as an immunomodulator to investigate its effects on mouse splenic B cells stimulated with the TLR9 agonist CpG ODN, either alone or in combination with antigen, and to explore its underlying mechanisms. The results showed that S2 had a significant negative regulatory effect on CpG ODN induced B cell activation. It also significantly downregulated the production of IL-6 and the percentage of IL-6 + B cells in splenocytes stimulated by CpG ODN, but significantly upregulated the percentage of IL-10 + B cells. Interestingly, S2 impaired antibody production both in vitro and in vivo, but rescued mice from lethal inflammatory responses. Further studies showed that S2 could bind IRF4 and IRF8 with high affinity, slightly upregulate phosphorylated IRF4, reduce the expression and nuclear translocation of IRF8, and alter the proportion of IRF4 + , IRF8 + or double-positive B cells in spleen cells induced by CpG ODN. These results suggest that S2 acts as a decoy directing some B cells to differentiate into IL-10-producing Breg-like cells rather than plasma cells by restoring the TLR9 signal-induced IRF4 and IRF8 ratio imbalance. This indicates its potential as an immunomodulator for the treatment of diseases associated with B-cell abnormalities.
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PubMed
高影响因子
Nano Research
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2021
·Vol. 15
·期 2
·1183-1192
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IF 8.897
Xu Yudi,Ma Sheng,Zhao Jiayu,Si Xinghui,Huang Zichao,Zhang Yu,Song Wantong,Tang Zhaohui,Chen Xuesi
Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death (ICD), which provides a promising alternative way for cancer immunotherapy. However, the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone. Herein, we proposed a trinity immune enhancing nanoparticles (TIENs) for boosting antitumor immune responses of chemo agents. The TIENs was constructed with Food and Drug Administration (FDA) approved polylactic acid (PLA), canonical proton-sponging cationic polymer polyethyleneimine (PEI), and Toll-like receptor 9 (TLR9) agonist cytosine phosphate guanine oligodeoxynucleotide (CpG-ODN). In in vitro studies, the TIENs was proved to (1) promote antigen capturing, (2) antigen-presenting cells (APCs) activation, and (3) antigen cross-presentation. In in vivo studies, intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models, respectively. Furthermore, after decoration with a detachable shielding, the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection. The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.
研究领域:
癌症免疫疗法
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纳米医学
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化疗
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免疫学
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DOI
高影响因子
ACS Nano
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2022
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IF 18.027
Zhijin Fan,Yichao Wang,Lanqing Li,Fanchu Zeng,Qiuping Shang,Yuhui Liao,Changhong Liang,Liming Nie
Many studies have focused on developing effective therapeutic strategies to selectively destroy primary tumors, eliminate metastatic lesions, and prevent tumor recurrence with minimal side effects on normal tissues. In this work, we synthesized engineered cellular nanovesicles (ECNVs) with tumor-homing and immune-reprogramming functions for photoacoustic (PA) imaging-guided precision chemoimmunotherapy. M1-macrophage-derived cellular nanovesicles (CNVs) were loaded with gold nanorods (GNRs), gemcitabine (GEM), CpG ODN, and PD-L1 aptamer. The good histocompatibility and tumor-homing effect of CNVs improved drug retention in the bloodstream and led to their enrichment in tumor tissues. Furthermore, the photothermal ability of GNRs enabled PA imaging-guided drug release. GEM induced tumor immunogenic cell death (ICD), and CpG ODN promoted an immune response to the antigens released by ICD, leading to long-term specific antitumor immunity. In addition, the PD-L1 aptamer relieved the inhibitory effect of the PD1/PD-L1 checkpoint on CD8+ T-cells and augmented the immunotherapeutic effect. The synergistic innate and adaptive immune responses enhanced the antitumor effect of ECNVs. In summary, this nanoplatform integrates local targeted photothermal therapy with extensive progressive chemotherapy and uses ICD to reshape the immune microenvironment for tumor ablation.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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生物医学工程
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诊疗学
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Yang Sui,Ji Li,Jiqiang Qu,Ting Fang,Hongyan Zhang,Jian Zhang,Zheran Wang,Mingyu Xia,Yinghui Dai,Dongkai Wang
Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years. A major challenge of cancer vaccine is to target cytosols of dendritic cells (DCs) in the lymph nodes (LNs) to enhance efficiency of antigen cross-presentation, which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells. Here, we address this issue by conjugating ovalbumin (OVA) to PEG-PCL using disulfide bond (-ss-), and the degradable pH-responsive polymer-PEI-PCL as delivery carrier. In addition, the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs. Subsequently, CpG ODN 1826 , a TLR-9 agonist, was further introduced into a mixed micelle of 30 nm or less as a unique tumor vaccine. Importantly, the results demonstrated the mixed micelles with 1:1 mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs, meanwhile, OVA was modified to the surface of mixed micelles via disulfide bonds (-ss-) for promotion efficiency of antigen cross-presentation. More surprisingly, combination of tumor vaccine with anti-PD-1, the therapy of ectopic melanoma (B16-OVA) and lung metastasis melanoma (B16-OVA) is excellent therapeutic effect. Taken together, our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.
研究领域:
癌症免疫学
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纳米技术
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药物递送系统
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免疫治疗
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产品关联
DOI
PubMed
高影响因子
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