WOUND REPAIR AND REGENERATION
·
2022
·Vol. 30
·期 3
·376-396
·
IF 3.401
Peng Wang,Bin Yin,Zexin Zhang,Shuting Mao,Wu Bao,Wenqin Lian,Yueying Fan,Chao Hong,Yingjun Su,Chiyu Jia
To characterise the distribution, classification, and quantity of foamy macrophages (FMs) in tuberculous wound tissue and the relationship between FM and delayed healing of tuberculous wounds. Morphological studies were performed to explore the distribution of FM and Mycobacterium tuberculosis (Mtb) in tuberculous wounds, with acute and chronic wounds included for comparison. Phorbol-12-myristate-13-acetate stimulation-differentiated THP-1 cells were treated with Mtb to induce their differentiation into FM with oxidised low-density lipoprotein treatment serving as a control. Relative cytokine levels were determined by quantitative PCR and Western blotting. Varied co-culture combinations of Mtb, THP-1, FM, and fibroblasts were performed, and proliferation, migration, ability to contract collagen gel, and protein levels of the chemokines in the supernatants of the fibroblasts were assessed. The differentially expressed genes in human skin fibroblasts (HSFs) after co-culture with or without FM were identified using microarray. Many FM were found in the tissues of tuberculous wounds. The FM that did not engulf Mtb (NM-FM) were mainly distributed in tissues surrounding tuberculous wounds, whereas the FM that engulfed Mtb (M-FM) were dominantly located within granulomatous tissues. Co-culture experiments showed that, with the Mtb co-culture, the portions of NM-FM in the total FM grew over time. The migration, proliferation, chemokine secretion, and the ability of fibroblasts to contract collagen gel were inhibited when co-cultured with Mtb, FM, or a combination of the two. Further investigation showed that the TLRs/NF-κB signalling pathway is involved in fibroblast function under the stimulation of FM. TLRs and NF-κB agonists could reverse the phenotypic changes in HSFs after co-culture with FM. The tuberculous wound microenvironment composed of Mtb and FM may affect wound healing by inhibiting the functions of fibroblasts. FM potentially inhibit fibroblasts' function by inhibiting the TLRs/NF-κB signalling pathway in tuberculous wounds.
研究领域:
免疫学
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微生物学
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病理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 5
·2118
·
IF 4.9
Xiyue Wang,Miaoyunhuan Wang,Yuqing Dong,Shuqing Yu,Shanshan Zhang,Pinghua Sun,Lu Wang,Jibin Liu,Houwen Lin,Xinhui Pan,Xiaobin Li
Chenopodium albumL., as a folkloric herb, is traditionally used to treat poisonous insect bites, vitiligo, and other ailments. However, its impact on thrombosis remains unknown. In this study, we discovered that the ethanol extract ofC. albumexhibited a remarkable antithrombotic effect using a zebrafish thrombosis model for the first time. Activity evaluation showed that fraction CA-C could improve thrombus aggregation in the caudal vein, increase blood return in the heart, and alleviate the slowing of blood flow compared with those in the model group. Then, analysis by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass (UPLC-Q-TOF-MS) identified 58 constituents of CA-C, with most of them belonging to flavonoids, alkaloids, and steroidal saponin components. Moreover, using a comprehensive strategy of network pharmacological analysis, transcriptomic assay, and RT-qPCR validation, we found that CA-C could mediate the TLR’s signaling pathway and its downstream MAPKs and PI3K/AKT signaling pathways to exert an antithrombotic effect. This study broadens the clinical application of plantC. albumand provides new insight into the chemical profile, pharmacodynamics, and potential mechanisms of CA-C as candidate agents for treating thrombosis.
研究领域:
药理学
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植物化学
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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 NANOBIOTECHNOLOGY
·
2026
·
IF 15
Yuzhi Qiu,Yunting Liu,Sihan Chen,Yidi Liu,Xi Yu,Xiangliang Yang,Yan Zhang,Yanhong Zhu
Reprogramming tumor-associated macrophages (TAMs) from the pro-tumoral M2-like state to the immunostimulatory M1-like phenotype has emerged as a promising strategy for tumor therapy. However, most M2-like TAMs are preferentially located in hypoxic regions of the tumor, which are poorly accessible to many advanced drug delivery systems, posing a significant challenge to effective TAM reprogramming. Here, leveraging the tropism of facultative anaerobic bacteria to localize and propagate in the hypoxic tumor, an optogenetically engineered Escherichia coli Nissle 1917 strain conjugated with murine STING agonist (EcN flaB @UPD) was developed for cancer-specific immunotherapy. Upon near-infrared light illumination, the blue and UV emissions from upconversion nanoparticles (UCNPs) simultaneously activate the expression of Toll-like receptor (TLR) agonist, flaB, from EcN flaB , and the release of photocaged murine STING agonist, DMXAA, respectively. This spatiotemporally synchronized dual release ensures co-localized STING and TLR5 agonists inside the hypoxic niche, repolarizing TAMs from the M2 to the M1 phenotype via synergistic TLR5-MAPK1-NF-κB and STING-NF-κB signaling. The polarization of TAMs enhances their antigen-presenting capacity and, more importantly, activates the cytotoxic, stem-like and memory CD8 + T cells responses. This subsequently inhibits tumor growth, relapse, and metastasis in the murine 4T1 tumor model. Collectively, our work introduces the bacteria-based system that uses near-infrared light to dual-release immunotherapeutics for systemic anti-tumor immunity, opening new avenues for precise and effective cancer immunotherapy.
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DOI
PubMed
高影响因子
3 Biotech
·
2020
·Vol. 10
·期 8
·1-10
·
IF 1.798
Ge Xin,Meng Xianglin,Fei Dongsheng,Kang Kai,Wang Qiubo,Zhao Mingyan
Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically.
研究领域:
药理学
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免疫学
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肺病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiao-Jun Li,Shi-Jun Xiao,Yi Heng Xie,Jiang Chen,Hai-Rong Xu,Yuan Yin,Rui Zhang,Tong Yang,Tong-Yu Zhou,Si-Yan Zhang,Pei Hu,Li-Ming Gao,Hui-Ping Peng
An innovative acidic hydrolysate fingerprinting workflow was proposed for the characterization of Lyophyllum Decastes polysaccharide (LDP) by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The crude polysaccharides were firstly separated and purified by using DE-52 column and the BRT GPC purification system, respectively. The molecular weight and monosaccharide content of homogeneous polysaccharides were ascertained by utilizing HPGPC and ion chromatography separately. Secondly, the linkage of LDP was identified by methylation analysis and 1D/2D NMR spectra. The UPLC-MS/MS was used to scan and identify the acidic hydrolysate products of LDP using the PGC column. The oligosaccharides were collected by chromatography and identified by mass spectrometry. Thirdly, the expression of IL-1β, IL-6, iNOS, TNF-α and IFNAR-I was measured in order to assess the immunological activity of LDP. Besides, the targeted receptors identification of polysaccharides was performed by screening the expression of TLRs family protein. The results showed that oligosaccharide fragments with different molecular weights can be obtained by partial hydrolysis, which further verified that the structures of LDP polysaccharides was a 1–6-linked β-glucan. Moreover, the LDP polysaccharide can up-regulate the content of IL-1β, IL-6, iNOS, TNF-α and IFNAR-I and plays an important immunoregulation role through TLRs family.
研究领域:
生物化学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2020
·
IF 1.813
Kai-hui Zhang,Mei-qi Wang,Lu-ling Wei,Cheng-jing Feng,Yu-si Zhang,Jian-bei Teng
Objective. Gout is a chronic disease that causes inflammatory arthritis, which is closely related to urate accumulation induced by a disorder of uric acid metabolism and the consequent deposition of monosodium urate crystals. Dendrobium loddigesii Rolfe is an herbal medicine that has been used in some traditional Chinese medicine formulae in the treatment of gout. This study aimed to explore and verify the antigout activity of Dendrobium loddigesii extract (DLE) on alleviating the hyperuricaemia of mice and the acute gouty arthritis of rats. Methods. An animal model of hyperuricaemia was established using potassium oxonate (PO). We analysed the expression of uric acid transporter mRNA in the kidney in the hyperuricaemic mice after treatment with DLE. Simultaneously, a monosodium urate crystal-induced acute gouty arthritis rat model was used to evaluate the effects of DLE, according to the level of ankle swelling, as well as the protein levels of inflammatory receptors and cytokines, as assayed by WB and ELISA. Results. DLE alleviated hyperuricaemia in mice and inhibited acute gouty arthritis in rats (). Meanwhile, DLE regulated the levels of uric acid transporters mRNA transcripts, including mouse organic anion transporter 1 (mOAT1), organic anion transporter 3 (mOAT3), urate transporter 1 (mURAT1), and glucose transporter 9 (mGLUT9) in the kidney (), suggesting that DLE promoted uric acid metabolism. Furthermore, DLE significantly suppressed the protein levels of TLRs, MyD88, and NF-κB in the ankle joint’s synovium (), and the serum levels of IL-1β, IL-6, and TNF-α were also reduced, which demonstrated the anti-inflammatory effects of DLE. Conclusion. DLE alleviates hyperuricaemia by regulating the transcription level of uric acid transporters in the kidney. It also inhibits acute gouty arthritis by inhibiting the pathway of TLRs/MyD88/NF-κB in the ankle joint’s synovium. The findings of the present study imply that DLE alleviates gout by promoting uric acid metabolism and inhibiting inflammation related to the TLRs/MyD88/NF-κB pathway.
研究领域:
药理学
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免疫学
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中医
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DOI
PubMed
高影响因子
BMC INFECTIOUS DISEASES
·
2025
·Vol. 25
·期 1
·1-16
·
IF 3
Lv Jiangbo,Wan Haofang,Yu Daojun,Zhou Huifen,Wang Wenba,Wan Haitong
ObjectivePenicillin-resistant Streptococcus pneumoniae (PRSP), for which novel treatment medicines are required, has expanded extensively due to the overuse of antibiotics. This study aimed to detect the optimal ratio of the combination of the main components based on Yinhuapinggan granules (YHPG) to generate novel treatment concepts for PRSP-induced lung injury.Methods Three representative main components: chlorogenic acid (C), amygdalin (A), and puerarin (P) were selected, and the optimal combination of these three components was determined by an orthogonal experiment. Investigations were conducted on the potential mechanisms underlying the protective effect of this optimized combination against PRSP-induced lung epithelial cell damage. Meanwhile, the bacteriostatic effect was further explored through the optimized combination of these natural products combined with penicillin G (PG).Results The optimized combination CAP (C: 16 µg/mL, A: 24 µg/mL, P: 24 µg/mL) screened by the orthogonal experimental design reduced cell damage in a model of human lung epithelial cells infected by PRSP, and the combination of CAP and PG had a synergistic effect. At the cellular level, CAP attenuated lung epithelial cell injury by modulating the TLRs/MyD88 inflammatory pathway. At the bacterial level, CAP modulated the virulence and drug resistance of PRSP, resulting in enhanced bacterial inhibition by the combination of CAP and PG.Conclusion Taken together, our results suggest that CAP can modulate or synergize with PG to modulate the TLRs/MyD88 pathway and attenuate PRSP-induced lung injury, and can be used as a potential drug for treating PRSP infection.
研究领域:
医学
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药理学
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感染性疾病
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中药研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Ruyi Chen,Fenfen Li,Kai Zhou,Mengyu Xing,Xiaoxi Zhang,Xinyu Zhao,Chenxi Wu,Ziwei Han,Yixuan Zhou,Li Yan,Daozong Xia
Ethnopharmacological relevance Modified sanmiao pills (MSMP), a traditional Chinese medicine (TCM) formula, is consisted of rhizome of Smilax glabra Roxb., Cortexes of Phellodendron chinensis Schneid., rhizome of Atractylodes chinensis (DC.) Koidz., and roots of Cyathula officinalis Kuan. in a ratio of 3:3:2:1. This formula has been broadly applied to treat gouty arthritis (GA) in China. Aims of the study To elaborate the pharmacodynamic material basis and pharmacological mechanism of MSMP against GA. Materials and methods UPLC-Xevo G2-XS QTOF combined with UNIFI platform was applied to qualitatively assess the chemical compounds of MSMP. Network pharmacology and molecular docking were used to identify the active compounds, core targets and key pathways of MSMP against GA. The GA mice model was established by MSU suspension injecting into ankle joint. The swelling index of ankle joint, expressions of inflammatory cytokines, and histopathological changes in mice ankle joints were determined to validate the therapeutic effect of MSMP against GA. The protein expressions of TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome in vivo was detected by Western blotting . Results In total, 34 chemical compounds and 302 potential targets of MSMP were ascertained, of which 28 were overlapping targets pertaining to GA. 143 KEGG enrichment pathway were obtained, of which the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, and NF-κB signaling pathway were strongly associated with GA. In silico study indicated that the active compounds had excellent binding affinity to core targets. In vivo study confirmed that MSMP observably decreased swelling index and alleviated pathological damage to ankle joints in acute GA mice. Besides, MSMP significantly inhibited the secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α) induced by MSU, as well as the expression levels of key proteins involved in TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome. Conclusion MSMP possessed a pronounced therapeutic effect on acute GA. Results from network pharmacology and molecular docking showed that obaculactone, oxyberberine, and neoisoastilbin might treat gouty arthritis by down-regulating TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome.
研究领域:
药理学
·
中药学
·
网络生物学
·
分子生物学
·
炎症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yaming Yu,Ningning Mao,Lin Yu,Fangzhu Lin,Xiaofeng Shi,Xuanqi Lu,Yang Yang,Yu Lu,Deyun Wang
Ethnopharmacological relevance Endometritis is a common reproductive disease in dairy cattle after calving, characterized by persistent inflammation of the endometrium. YiMu-QingGong San (YMQGS), a patented Chinese medicine formulation, has demonstrated efficacy in the treatment of clinical endometritis in dairy cattle. However, the potential mechanisms by which YMQGS alleviates endometritis remain unclear. Aim of the study The objective of this study is to elucidate the underlying therapeutic mechanisms of YMQGS in the context of endometritis. Materials and methods The chemical components of YMQGS were analyzed using UHPLC/MS. The anti-inflammatory capabilities of YMQGS were assessed by inducing an inflammatory response in RAW264.7 cells with lipopolysaccharide (LPS). Moreover, a clinical model of endometritis was simulated via vaginal injection of LPS into the uterine horns to investigate the therapeutic mechanisms of YMQGS. Results YMQGS could downregulate the expression of inflammatory mediators (TNF-α, IL-6, IL-1β) by suppressing the activation of the TLRs/MyD88/TRAF6/NF-κB signaling pathway in RAW264.7 cells. Additionally, YMQGS facilitated the polarization of RAW264.7 cells towards M2-like macrophages (Mφs) while inhibiting M1-like Mφs polarization, thereby exerting anti-inflammatory effects. Further investigation revealed that YMQGS could diminish ROS production, augment cellular antioxidant capacity, preserve mitochondrial membrane potential, and reduce intracellular [Ca 2+ ]i accumulation, thereby minimizing cellular damage. In the mouse model of endometritis, YMQGS similarly inhibited the activation of the NF-κB signaling pathway in uterine tissues and modulated Mφ polarization in the endometrium, leading to a decrease in the expression of inflammatory factors and subsidence of the inflammatory response in the endometrium. Histological staining results showed that YMQGS reduced endometrial fibrosis, increased the expression of endometrial ZO-1, Occludin and glycoprotein, protect the endometrial barrier function, and prevent the further development of endometritis. Conclusion Collectively, the present study confirms that YMQGS possesses notable anti-inflammatory and antioxidant properties. The suppression of the NF-κB signaling pathway and the modulation of Mφ polarization emerge as the pivotal mechanisms by which YMQGS alleviates endometritis.
研究领域:
药理学
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免疫学
·
生殖医学
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中医药
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2021
·
IF 4.219
Huilong Xiang,Huan Lei,Ziyuan Liu,Yongjie Liu,Yang Li,Yinsheng Qiu,Lingyun Xu
Oxidative stress and inflammation in kidney are the main causes for hyperuricemic nephropathy (HN). Baicalin and baicalein , two flavonoids , have anti-inflammatory and anti-oxidative effects and they are interconvertible in the body. In this study, both baicalin and baicalein were administered by intragastric administration (i.g.) or intraperitoneal injection (i.p.) at the dose of 50 mg kg −1 , once a day for 15 consecutive days to HN mice, a model established by i.g. of yeast extract combined with i.p. of potassium oxonate . In HN mice, baicalin and baicalein reduced serum uric acid (SUA) levels and protected kidneys by anti-inflammatory and anti-oxidative effects. Mechanistically, the effect of baicalin and baicalein on reducing SUA levels might due to their inhibitory effect on xanthine oxidase (XO) activity in vivo and in vitro . Furthermore, the mechanisms of baicalin and baicalein against HN were analyzed with network pharmacology and molecular docking technology . The network pharmacology indicated that the protective effects of baicalin and baicalein against HN were mainly related to their down-regulating effects on TLRs , NF-κB, MAPK, PI3K/AKT and NOD-like receptor signaling pathways. Molecular docking indicated high binding affinity of baicalin/baicalein to targets such as AKT1 and MAPK1 . In summary, baicalin and baicalein are promising drug candidates for the treatment of HN by inhibiting XO activity, reducing inflammation and cell apoptosis through down-regulating TLRs/NLRP3/NF-κB, MAPK, PI3K/AKT/NF-κB pathways.
研究领域:
药理学
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分子生物学
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肾病学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Fangfang Min,Jielun Hu,Tao Huang,Yousheng Huang,Shaoping Nie,Tao Xiong,Mingyong Xie
Lactobacillus ( L. ) casei NCU011054 isolated from infant feces has been proven to be a potential probiotic in vitro . The present study aimed to investigate the effects of L. casei NCU011054 on the immune response and gut microbiota in cyclophosphamide (CP)-induced immunosuppression mice. Results indicated that L. casei NCU011054 could increase the levels of mucin (Muc2) and tight junction proteins (ZO-1, occludin and claudin-1). Moreover, L. casei NCU011054 was found to upregulate TLRs/NF-κB pathway (TLR-2, TLR-4, TLR-6, p65 and NF-κB) and two transcription factors (T-bet and GATA-3) mRNA levels, and enhance the number of CD4 + T cells. Th1-related cytokines (IL-12p70, IFN-γ and TNF-α) and Th2-related cytokines (IL-2, IL-4, IL-6 and IL-10) significantly increased after L. casei NCU011054 treatment. More importantly, L. casei NCU011054 increased the ratio of T-bet to GATA-3 and IFN-γ to IL-4. Apart from these, L. casei NCU011054 remodeled gut microbiota and modulated gut metabolites in CP-induced immunosuppressed mice. The correlation analysis showed that Lactobacillus upregulated by L. casei NCU011054 was positively correlated with TLRs/NF-κB pathway, and the ratio of T-bet to GATA-3 and IFN-γ to IL-4. All findings revealed that L. casei NCU011054 could improve intestinal immune dysfunction and modulate Th1/Th2 balance via TLRs/NF-κB pathway in CP-induced immunosuppressed mice.
研究领域:
免疫学
·
微生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Nano Research
·
2022
·Vol. 15
·期 9
·8326-8335
·
IF 10.269
Li Xiangxia,Chen Guiyuan,Wang Yangyi,Su Lanhong,Chen Bo,Wu Kecheng,Xing Yun,Song Zechenxi,Dai Ruike,Liu Tianxin,Zhao Jiaao,Xie Zhe,Zhou Peijie,Xia Xiaoping,Min Yuanzeng
In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNs@Lipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy.
研究领域:
免疫学
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纳米医学
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肿瘤学
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药学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）