JOURNAL OF ETHNOPHARMACOLOGY
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2023
·
IF 5.4
Yang Gao,Shi-Qiao Liu,Jia-Long Wang,Han-Ming Cui,Qiu-Yan Zhang,Lei Wang,Yi-Xin Zhang,Jian Li,Yu Dong,Yuan-Hui Hu
Ethnopharmacological relevance Sanhuang Xiexin Decoction (SHXD), consisting of Coptis chinensis Franch., Scutellaria baicalensis Georgi and Rheum palmatum L. , is t raditionally used for relieving fever, purging fire for removing toxins, eliminating phlegm and haemostasis, eliminating the wetness-evil from the upper warmer, clearing away the heat-evil and expelling superficial evils. Each of the three herbs contained in SHXD has been indicated to have anti-inflammatory effects in vivo , but its effects on rat NK-cell phenotypes remain unexplored, and the comprehensive mechanism of this compound SHXD in curing the inflammation induced by lipopolysaccharides (LPS) remains to be revealed. Aim of the study The study aim was to assess the effect of SHXD on LPS-induced fever and inflammation in a rat model, reduce NLRP3 activation in NK cells expressing specific cell phenotype antibodies and determine the therapeutic value of this approach in vivo . Materials and methods SHXD extract was prepared and analysed by the developed ultra-performance liquid chromatography (UPLC) method for the simultaneous detection of 14 compounds. The main peaks were firstly identified on an Orbitrap via high resolution tandem mass spectrometry (MS). Then, the extract was used in the rat model of LPS-induced inflammation and fever for pharmacologically study the effects of drug treatment. Peripheral blood lymphocyte cells were isolated from the animals, including those subjected to the SHXD extract treatment, and the cell phenotype was determined prior to cell culture and after treating the cell cultures with the extract. The phenotypes of cells harvested using CD3, CD4, CD8a, CD81, CD161 and CD86 antibodies were used to verify the enhanced memory of the peripheral blood lymphocytes cells (PBMC) that were induced into nature killer (NK) cells. Results The SHXD extract was prepared, analysed and identified via quality control equipment and was observed to have pharmacological effects that reduced NLRP3 activation and fever in rats. The production of NK cells and peripheral blood lymphocytes was induced by the SHXD extract, which manifested as increased levels of CD4 + , CD8a+, CD81 + , CD161+ and CD86 + cells. The levels of CD3 + cells were significantly different between the model group and the drug-treated or control groups (p < 0.01) with dose independence, while the levels of CD4 + cells were not significantly different between the drug-treated and control groups, with a trend towards lower levels in the model group with dose independence. The levels of CD4 + cells was significantly different between the drug-treated group and the model groups with dose independence (p < 0.05). The levels of CD86 + cells were not significantly different between the drug-treated group and the model and control groups. The levels of CD8a + cells was significantly different between the model group and the drug and control groups (p < 0.05, dose 2.0 μg/ml), with higher levels in the drug-treated group. The levels of CD3 + , CD4 + , CD8a + cells in the drug treated group have dose dependence with SHXD. Conclusions This experiment revealed that SHXD reduced NLRP3 activation in the blood of LPS-treated rats, which occurred through the activation of NK cells that expressed CD3, CD8a and CD161. SHXD may possess anti-inflammatory effect via activacting the one of major pharmacology effcet of NK cells that expressed CD3, CD8a and CD161 phenotypes expression. This result demonstrates that SHXD may possess ability to enhance the memory of peripheral blood lymphocytes and natural killer cells.
研究领域:
药理学
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免疫学
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分析化学
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中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Wei Xu,Sijia Fang,Yong Wang,Xiaoqing Chi,Xiaodan Ma,Tao Zhang,Songhua Hu
The present study was to investigate the molecular mechanism underlying lymphocyte activation by total polysaccharides from Atractylodis macrocephalae (RAMPtp). The results showed that RAMPtp significantly promoted the secretions of cytokines (IFN-γ, IL-1α, IL-21, IFN-α, CCL4, CXCL9 and CXCL10), increased the proportions of CD4 + and CD8 + subpopulations, and enhanced the expressions of c-JUN, NFAT4, STAT1 and STAT3. microRNA sequencing identified 67 differentially expressed miRNAs (DEMs) in RAMPtp-stimulated SMLN lymphocytes, including 55 up-regulated and 12 down-regulated. GO and KEGG enrichment analyses of the predicted DEMs-targeted genes indicated that they were associated with immune system pathways, including PI3K-Akt, MAPKs, Jak-STAT and Calcium signaling pathways, which were confirmed by western blot and pathway inhibition assays. RAMPtp was further observed to favor immunostimulatory effect on both T and B lymphocytes via binding to TCR and membrane Ig individually. These findings might explain the immunomodulatory mechanism of RAMPtp in ameliorating the bovine intramammary infection.
研究领域:
免疫学
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分子生物学
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兽医学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
IMMUNOLOGY LETTERS
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2019
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IF 2.552
Gang Chi,Jin-hong Pei,Qin-ya Ma,Ying-Xia Ru,Zuo-hua Feng
Autoimmune hepatitis (AIH) is a chronic liver disease mediated by immunity, and could lead to liver fibrosis and hepatocellular carcinoma. However, the mechanisms for breaking hepatic tolerance and driving AIH still remain elusive. We herein reported that the non-specific liver inflammation triggered by carbon tetrachloride (CCl 4 ) recruited high numbers of CD4+T, CD8+T and B cells, and elevated the expression of proinflammaitory cytokines in Balb/c mice, further breaking liver tolerance and inducing autoimmune response, AIH inflammation and liver fibrosis in the presence of CYP2D6 antigen mimicry. In contrast, adenovirus infection could not break liver tolerance and induce AIH in Balb/c mice even in the presence of CYP2D6 antigen mimicry. These results suggested that genetic predisposition could determine liver tolerance in Balb/c mice. The chemical induced inflammation in the liver breaks tolerance and might be considered important for the initiation and development of AIH in Balb/c mice.
研究领域:
免疫学
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肝病学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-19
·
IF 10.2
Zhang Peisen,Cui Yingying,Wang Jian,Cheng Junwei,Zhu Lichong,Liu Chuang,Yue Saisai,Pang Runxin,Guan Jiaoqiong,Xie Bixia,Zhang Ni,Qin Meng,Jing Lihong,Hou Yi,Lan Yue
Background Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects.Results Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them.Conclusion The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.Graphical Abstract
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Guiyuan Chen,Xiangxia Li,Rui Li,Kecheng Wu,Zhouhang Lei,Ruike Dai,Kyle Roche,Andrew Z. Wang,Yuanzeng Min
Chemotherapeutics have the potential to increase the efficacy of cancer immunotherapies by stimulating the production of damage-associated molecular patterns (DAMPs) and eliciting mutations that result in the production of neoantigens, thereby increasing the immunogenicity of cancerous lesions. However, the dose-limiting toxicity and limited immunogenicity of chemotherapeutics are not sufficient to induce a robust antitumor response. We hypothesized that cancer cells in vitro treated with ultrahigh doses of various chemotherapeutics artificially increased the abundance, variety, and specificity of DAMPs and neoantigens, thereby improving chemoimmunotherapy. The in vitro chemotherapy-induced (IVCI) nanovaccines manufactured from cell lysates comprised multiple neoantigens and DAMPs, thereby exhibiting comprehensive antigenicity and adjuvanticity. Our IVCI nanovaccines exhibited enhanced immune responses in CT26 tumor-bearing mice, with a significant increase in CD4+/CD8+ T cells in tumors in combination with immune checkpoint inhibitors. The concept of IVCI nanovaccines provides an idea for manufacturing and artificial enhancement of immunogenicity vaccines to improve chemoimmunotherapy.
研究领域:
肿瘤学
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免疫学
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药学
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生物技术
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
·
IF 8.025
Panpan Song,Zhongxia Lu,Tianze Jiang,Wenwei Han,Xiangyan Chen,Xia Zhao
The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/ [email protected] ) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/ [email protected] are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4 + /CD8 + T cells by silencing PD-L1 expression. In vivo studies show that R/C/ [email protected] exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2023
·
IF 14.5
Hongjuan Zhao,Yatong Li,Beibei Zhao,Cuixia Zheng,Mengya Niu,Qingling Song,Xinxin Liu,Qianhua Feng,Zhenzhong Zhang,Lei Wang
Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4 + T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8 + T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.
研究领域:
免疫学
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纳米技术
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癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-14
·
IF 9.429
Deng Bo,Ma Bing,Ma Yingying,Cao Pei,Leng Xigang,Huang Pengyu,Zhao Yuanyuan,Ji Tianjiao,Lu Xueguang,Liu Lanxia
Chemotherapeutics that can trigger immunogenic cell death (ICD) and release tumor-specific antigens are effective on treating a variety of cancers. The codelivery of chemotherapeutics with adjuvants is a promising strategy to achieve synergistic therapeutic effect. However, low drug loading and complicated preparation of current delivery systems lead to carrier-associated toxicity and immunogenicity. Herein, we developed a facile approach to construct liposomal spherical nucleic acids (SNA) by the self-assembly of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)-doxorubicin conjugate and DOPE-matrix metalloproteinases-9 (MMP-9) responsive peptide-CpG conjugate (DOPE-MMP-CpG). Liposomal SNAs efficiently co-delivered DOX and CpG into tumors and released the two drugs upon biological stimuli of MMP-9 enzyme in tumor microenvironment (TME) and high concentration of endogenous glutathione in tumor cells. We demonstrated that liposomal SNA enhanced activation of dendritic cells (DCs), promoted expansion of CD8 + and CD4 + T cells in both tumors and spleen, inhibited tumor growth, and extended animal survival. This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors with synergistic therapeutic effect and reduced side effect. Graphical Abstract
研究领域:
癌症治疗
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药物递送系统
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免疫疗法
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纳米医学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2022
·
IF 10.633
Xinyao Feng,Fangshen Li,Liangliang Zhang,Wenmo Liu,Xupu Wang,Rui Zhu,Zhen-An Qiao,Bin Yu,Xianghui Yu
Traditional anticancer treatments directly target tumor cells. In contrast, cancer immunotherapy fortifies host immunity. Nanoparticles that incorporate both immunomodulatory and chemotherapeutic agents regulate the tumor microenvironment by activating immune cells and enhancing antitumor immunity. Nanoparticle-based cancer immunotherapy has received considerable attention and has been extensively studied in recent years. In this study, we developed a targeted drug delivery system to enhance immunotherapeutic efficacy and overcome drug resistance by inducing tumor apoptosis and immunogenic cell death (ICD), and activating immune cells. Periodic mesoporous organosilica nanoparticles (PMOs) bore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on their surfaces, and their inner cores were loaded with doxorubicin (DOX). TRAIL enhanced the nanoparticle-targeting capacity and worked synergistically with DOX against breast cancer cells in vitro and in vivo . Furthermore, we revealed for the first time the ability of PMOs to activate dendritic cells (DCs) and elevate ICD levels of DOX in vitro , and TRAIL further enhances the immunomodulatory function of PMOs. Systemic exposure to [email protected] induced an immune response, activated DCs and CD4 + and CD8 + T cells , and significantly suppressed tumor growth in a 4T1-bearing immunocompetent mouse model. Overall, our study demonstrates that TRAIL-modified, DOX-embedded PMO nanoparticles represent a good candidate for tumor-targeted immunotherapy, which has relatively superior therapeutic efficacy and highly promising future application prospects. Statement of significance This study revealed for the first time the ability of PMOs to elevate ICD levels and activate DCs in vitro . The results explained the immunomodulatory function of PMOs and demonstrated the synergistic effects of TRAIL and DOX in triple-negative breast cancer. In addition, immunomodulatory effects of the drug delivery vectors constructed in this study were verified in vivo .
研究领域:
癌症研究
·
纳米技术
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免疫疗法
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Meng He,Wei Xu,Yuxin Dan,Yue Pan,Yingying Li,Mingsheng Chen,Chang-Ming Dong
It is challenging for nanovaccines (NVs) to effectively deliver antigens/neoantigens to prime specifically potent immunities and remodel immunosuppressive tumor microenvironment (TME) for combating immune “cold” cancers. Herein, a novel kind of mannosylated fluoropolypeptide NVs of MFPCOFG (i.e., mannosylated fluoropoly( D,L -cysteine) ovalbumin-loaded Fe 2+ -gallic acid) is designed that synergistically integrates triple antigen-metal-thermoimmunity to remodel immunosuppressive TME and achieve highly potent immunities. MFPCOFG plus near-infrared irradiation (NIR) effectively facilitated antigen uptake and escape, induced the maturation and antigen cross-presentations of dendritic cells and macrophages, polarized anti-inflammatory macrophage phenotype M2 into tumoricial M1, primed potent CD4 + /CD8 + T cells responses, proinflammatory cytokines secretion and immune memory effects, showcasing triple antigen-metal-thermoimmunity outperforming combo/mono-immunity. Importantly, both MFPCOFG + NIR and personalized NVs can remarkably enhance the tumor infiltration of CD4 + /CD8 + T and NK cells to boost potent immunities and long-lasting memory effects, reduce regulatory T (Tregs) and M2 to remodel immunosuppressive TME in B16-OVA and 4T1 models, achieving superior tumor prevention, ablation, and tumor relapse and metastasis inhibition, as further orchestrated with anti-PD-1. Consequently, this work opens up a new avenue to design biocompatible polypeptide nanovaccines with potent immune-priming and TME-remodeling capabilities, holding great potentials to combat immune “cold” cancers with clinic-used anti-PD-1 for cancer immunotherapy and personalized immunotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Dingkun Liu,Jinbing Chen,Linjuan Gao,Xing Chen,Liujun Lin,Yuan Liu,Xia Wei,Yu Pan,Yinghui Wang,Hui Cheng
Dental implant restoration has become one of the most important treatments for missing teeth. However, peri-implantitis is a common complication of implant restorations, and lack of timely and effective treatment will most likely lead to implant failure. Here, we developed a chitosan-based multifunctional temperature-sensitive hydrogel. Chitosan (CS)/β-glycerophosphate (β-GP) as the body of the hydrogel enabled a gelation transition at physiological temperatures. To enhance functionality, we designed Sim@ZIF8@PDA nanoparticles (SZP), where simvastatin (Sim) was loaded onto the zeolitic imidazolate framework-8 (ZIF8), leveraging its high drug-loading capacity and pH-sensitive release properties. These nanoparticles were further coated with polydopamine (PDA) to enhance photothermal efficiency and stability. The SZP nanoparticles were subsequently integrated with CS/β-GP to form the SZP/CS/β-GP hydrogel. The results showed that under near-infrared light irradiation, PDA exerted a photothermal effect to achieve anti-infection, while the release of simvastatin could promote the differentiation of CD4+ T cells to regulatory T cells (Tregs) to achieve immunoregulation. SZP/CS/β-GP hydrogel attenuated the infection and inflammation at the peri-implantitis lesion. In conclusion, this study provides a new approach for the non-surgical treatment of peri-implantitis.
研究领域:
牙科材料
·
纳米医学
·
药剂学
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再生医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chen Xinlu,Gong Luyao,Wang Yuanyuan,Ye Chen,Guo Huanhuan,Gao Shen,Chen Jiyuan,Wang Zhuo,Gao Yuan
Introduction: Metastatic castration-resistant prostate cancer (mCRPC) patients face challenges due to limited treatment options. About 50% of patients with mCRPC have a functional loss of phosphatase and tensin homology deleted on chromosome 10 (PTEN), leading to tumor progression, metastasis, and immune suppression. Moreover, elevated IL-23 produced by myeloid-derived suppressor cells (MDSCs) is found in CRPC patients, driving tumor progression. Therefore, a combination strategy based on PTEN restoration and IL-23 inhibition may block CRPC progression and metastasis.Methods: The antitumor effect of restoring PTEN expression combined with the IL-23 inhibitor Apilimod was studied in a mouse model of bone metastasis CRPC and mouse prostate cancer RM-1 cells. To verify the targeting ability of PTEN DNA coated with lipid nanoparticles (LNP@PTEN) in vitro and in vivo. In addition, RT-qPCR and flow cytometry were used to investigate the related mechanisms of the antitumor effect of LNP@PTEN combined with Apilimod.Results: LNPs exhibited significant tumor-targeting and tumor accumulation capabilities both in vitro and in vivo, enhancing PTEN expression and therapeutic efficacy. Additionally, the combination of LNP@PTEN with the IL-23 inhibitor Apilimod demonstrated enhanced inhibition of tumor growth, invasion, and metastasis (particularly secondary organ metastasis) compared to other groups, and extended the survival of mice to 41 days, providing a degree of bone protection. These effects may be attributed to the PTEN function restoration combined with IL-23 inhibition, which help reverse immune suppression in the tumor microenvironment by reducing MDSCs recruitment and increasing the CD8+/CD4+ T cell ratio.Discussion: In summary, these findings highlight the potential of LNPs for delivering gene therapeutic agents. And the combination of LNP@PTEN with Apilimod could achieve anti-tumor effects and improve tumor microenvironment. This combinational strategy opens new avenues for the treatment of mCRPC.
研究领域:
肿瘤学
·
分子生物学
·
纳米技术
·
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）