Science Advances
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2024
·Vol. 10
·期 26
·
IF 11.7
Ruifeng Luo,Jinwei Liu,Qian Cheng,Mitsuhiko Shionoya,Cheng Gao,Ruibing Wang
Oral medication for ulcerative colitis (UC) is often hindered by challenges such as inadequate accumulation, limited penetration of mucus barriers, and the intricate task of mitigating excessive ROS and inflammatory cytokines. Here, we present a strategy involving sodium alginate microspheres (SAMs) incorporating M2 macrophage membrane (M2M)–coated Janus nanomotors (denominated as Motor@M2M) for targeted treatment of UC. SAM provides a protective barrier, ensuring that Motor@M2M withstands the harsh gastric milieu and exhibits controlled release. M2M enhances the targeting precision of nanomotors to inflammatory tissues and acts as a decoy for the neutralization of inflammatory cytokines. Catalytic decomposition of H2O2 by MnO2 in the oxidative microenvironment generates O2 bubbles, propelling Motor@M2M across the mucus barrier into inflamed colon tissues. Upon oral administration, Motor@M2M@SAM notably ameliorated UC severity, including inflammation mitigation, ROS scavenging, macrophage reprogramming, and restoration of the intestinal barrier and microbiota. Consequently, our investigation introduces a promising oral microsphere formulation of macrophage-biomimetic nanorobots, providing a promising approach for UC treatment.
研究领域:
药学
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纳米技术
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胃肠病学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Shudan Zheng,Zhenghao Zhou,Jie Ji,Yuxin Liu,Xiaodan Jiao,Xiaoyang Li,Yi Shen,Hao Hong,Xiaodong Han
Idiopathic pulmonary fibrosis (IPF) exhibits extremely high mortality rates. Targeted therapy, which utilizes specific drugs or other substances to identify and attack specific molecular targets in the lesion, holds promise as a potent means of treating IPF. M2 macrophages have been shown to express high levels of osteopontin (OPN) early in the onset of IPF and sustain this high expression to promote the progression of IPF. Intervention in OPN expression can effectively impede the development of fibrosis. While the technology for targeting proteins with siRNA has become increasingly mature, the targeted delivery of siRNA to resident M2 macrophages in the lungs remains challenging. In this study, we developed an engineered self-assembling OPN siRNA carrier complex based on a metal-polyphenol network (luteolin-Zr) and PEG conjugated with an M2 macrophage-targeting peptide (Pery-PEG-M2), termed siOPN@LuZ-M2, for the treatment of pulmonary fibrosis. Consequently, significant therapeutic effects were observed in both bleomycin-induced pulmonary fibrosis mouse models and human precision-cut lung slices (hPCLS) models. Importantly, luteolin, which is slowly released from siOPN@LuZ-M2 within cells, can gradually accumulate in fibrotic lung tissue, exerting an anti-inflammatory effect and further enhancing the treatment of IPF. It is worth mentioning that siOPN@LuZ-M2 can be labeled with 89 Zr, allowing for the detection of its in vivo distribution and metabolic behavior via PET-CT. This study presents a promising new image-guided molecular targeting strategy for the treatment of fibrosis.
研究领域:
药理学
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分子生物学
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医学影像学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
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IF 4.8
Qian Feng,Cai-Zhi Li,Yi-Hua Zou,Xue-Yu Wang,Xia Yang,Rong Zhang*,Zhong-Qiu Liu*,Rong-Rong Zhang
Introduction: Brain metastasis (BM) is the most common and serious complication of breast cancer (BC). There is significant interest in investigating the crosstalk between BC cells and immune cells. β-elemene is the main pharmacodynamic component of Curcumae Rhizoma, a traditional Chinese medicine that is commonly used for the clinical treatment and prevention of various tumors. However, the specific underlying mechanism of β-elemene in BC-BM is still unclear.Methods: An intracardiac (ICT) injection model was used to establish specific BC-BM cells, then an intracarotid (ICD) injection model was used to verify the inhibitory effect of β-elemene in BC-BM. Tumor-cell-conditioned media, a primary microglia co-culture model, and an in vitro recruitment experiment were used to explore crosstalk between BC cells and immune cells. TMT-based quantitative proteomic, ELISA, IF, and other molecular biotechnologies were used to investigate the mechanisms.Results: The BC-BM cells established in our study not only increased BM rates but also exhibit mesenchymal phenotype and activated the JAK–STAT signaling pathway. Microglia, particularly M2 microglia, were enriched in BM lesions and secreted high levels of both IL6 and CCL2. Hypersecretory IL6 reversed the MET process of BC cells by regulating the JAK2/STAT3 signaling pathway to promote colonization in the brain. Increased levels of CCL2 significantly recruited monocytic myeloid-derived suppressor cells (M-MDSCs) to induce an immunosuppressive brain microenvironment. β-elemene could significantly inhibit BC-BM in mice by regulating the IL6/STAT3 signaling pathway and suppressing the M-MDSC recruitment.Conclusion: Our work first demonstrated that β-elemene regulated the IL6/STAT3 axis and M-MDSC recruitment to reconstruct immunosuppressive brain microenvironment to suppress BC-BM.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Shukun Zhao,Qiong Jiang,Ling Yu,Quan Liu,Zi Chen,Danting Zhan,Shuyu Chen,Yuqiong Yang,Jiacheng Zhong,Bingxin Guo,Fei Shi,Rongchang Chen,Lingwei Wang,Lang Rao,Junxia Zheng,Qian-Fang Meng,Shanze Chen
Eosinophilic asthma is a chronic inflammatory disease driven by Type 2 immune cells and cytokines. While cytokine-based immunotherapies have shown promising efficacy in asthma treatment, current approaches often fail to simultaneously target multiple cytokines. In this study, we present nanodecoys derived from the cellular membranes of M2 macrophages, which exhibit a high density of cytokine receptors, enabling efficient sequestration of multiple Type 2 cytokines. This mechanism significantly alleviates OVA-induced eosinophilic asthma inflammation in mice. To enhance therapeutic efficacy, D-mannose glycans, a potential immunoregulatory molecule for asthma, were modified onto the surface of the nanovesicles. This modification facilitates the phagocytic clearance of absorbed cytokines by targeting the mannose receptor (CD206). Consequently, the mannose-modified nanovesicles exhibit synergistic immunosuppressive effects on asthmatic inflammation by inhibiting M2 macrophage polarization, CD4+ T cell Th2 polarization, and eosinophil activation, as revealed by single-cell RNA sequencing and in vitro analyses. In summary, this study presents a safe and effective nanotechnology-based immunotherapy for asthma and potentially other Type 2 inflammatory diseases.
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Chunyou Lai,Yunchao Yang,Pengfei Wei,Guangming Xiang,Guan Wang,Shasha Liu,Li Zeng,Guanghong Du,Ke Yang,Maozhu Yang,Xueying Zhang,Yunhuan Li,Xueqiao Yu,Bo Zhao,Yutong Yao
Pancreaticojejunostomy presents significant challenges due to the high risk of complications such as pancreatic leakage and poor tissue regeneration. However, current approaches to enhance surgical outcomes are often limited by issues related to biocompatibility, tissue repair efficacy, and inflammation modulation. Here, we report the potential of an adhesive polyethylene glycol (PEG) hydrogel incorporating M2 macrophage-derived exosomes (PEG/Exo M2 ) for improving tissue repair in pancreaticojejunostomy. M2 macrophage-derived exosomes exhibit potent anti-inflammatory properties and pro-angiogenic effects, making them ideal candidates for tissue regeneration. The PEG/Exo M2 hydrogel demonstrates excellent mechanical strength and strong antibacterial activity. In vitro assays reveal that the PEG/Exo M2 hydrogel promotes angiogenesis and cell migration while modulating inflammatory responses. In animal models, the PEG/Exo M2 hydrogel effectively reduces fibrosis and inflammation in a subcutaneous implantation model, and significantly improves tissue regeneration. In a pancreaticojejunostomy model, the PEG/Exo M2 hydrogel facilitates wound sealing, lowers the risk of pancreatic leakage, and enhances anastomotic repair, outperforming conventional sutures. These results highlight the PEG/Exo M2 hydrogel as a promising biomaterial for tissue repair and regeneration, with strong potential for clinical applications in surgical wound healing.
研究领域:
生物材料学
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再生医学
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外科手术
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DOI
高影响因子
CELLULAR SIGNALLING
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2023
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IF 4.8
Jinmiao Tian,Lichao Zhang,Xiaoqin La,Xiaxia Fan,Aiping Li,Changxin Wu,Yuxuan An,Shuning Yan,Xiushan Dong,Haitao Wu,Zhuoyu Li
Macrophages in hypoxic regions of advanced colorectal tumors often exhibit M2-type features, but prefer oxygen-consuming lipid catabolism , which is contradictory in oxygen demand and supply. In this study, the results from bioinformatics analysis and intestinal lesions immunohistochemistry of 40 colorectal cancer patients illustrated that glucose-regulatory protein 78 (GRP78) was positively correlated with M2 macrophages. Furthermore, tumor-secreted GRP78 could enter macrophages and polarize them to M2-type. Mechanistically, entered GRP78 located in lipid droplets of macrophages, and elevated protein stabilization of adipose triglyceride lipase ATGL by interacting with it to inhibit its ubiquitination . Increased ATGL promoted the hydrolysis of triglycerides and the production of arachidonic acid (ARA) and docosahexaenoic acid (DHA). Excessive ARA and DHA interacted with PPARγ to encourage its activation, which mediated the M2 polarization of macrophages. In summary, our study showed that secreted GRP78 in the tumor hypoxic microenvironment mediated the domestication of tumor cells to macrophages and maintained tumor immunosuppressive microenvironment by promoting lipolysis, and the lipid catabolism not only provides energy for macrophages but also plays an important role in maintenance of immunosuppressive properties.
研究领域:
肿瘤学
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免疫学
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细胞生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Junkai Zeng,Zhenyu Sun,Feihui Zeng,Changjiang Gu,Xiongsheng Chen
Due to local overactive inflammatory response and impaired angiogenesis, current treatments for diabetic wounds remain unsatisfactory. M2 macrophage-derived exosomes (MEs) have shown considerable potential in biomedical applications, especially since they have anti-inflammatory properties that modulate macrophage phenotypes. However, exosome-based strategies still have limitations, such as short half-lives and instability. Herein, we develop a double-layer microneedle-based wound dressing system ( [email protected] ) by encapsulating MEs in the needle tips and polydopamine (PDA) nanoparticles in backing layer to simultaneously suppress inflammation and improve angiogenesis at the wound site. In vitro , released MEs increased macrophage polarization towards the M2 phenotype. In addition, mild heat (40 °C) generated by the photosensitive PMN backing layer contributed to improved angiogenesis. More importantly, [email protected] also showed promising effects in diabetic rats. The uncontrolled inflammatory response at the wound site was inhibited by [email protected] during a 14-day period; in addition, MEs and the photothermal effects produced by PMN provided a combined proangiogenic effect by improving the expression of CD31 and vWF. Collectively, this study provides a simple and efficient cell-free strategy for suppressing inflammation and promoting vascular regeneration to treat diabetic wounds.
研究领域:
生物医学工程
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伤口愈合
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药学
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糖尿病研究
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 9
·期 7
·1867-1876
·
IF 5.344
Man Luo,Fujian Zhao,Lu Liu,Zhen Yang,Ting Tian,Xiaoyu Chen,Xiaodong Cao,Dafu Chen,Xiaofeng Chen
The macrophage-dominated bone immune response plays an important role in osteogenesis of bone defects. Generally, M2 macrophages are beneficial to promote osteogenesis. However, recent studies have confirmed that M1 also plays an important role in early angiogenesis, osteointegration. Therefore, achieving sequential polarization of macrophages from M1 to M2 may be more beneficial for osteogenesis. In this study, a new type of bone immunomodulatory IFN-γ/Sr-dropped bioactive glass composite scaffold (IFN-γ/SrBG) was successfully prepared which integrates multiple biological functions at different stages of the bone healing process. The scaffold can polarize macrophages into pro-inflammatory M1 type at the early stage of implantation by releasing IFN-γ within the first day, and then polarize macrophages into anti-inflammatory M2 type at a later stage by releasing Sr2+ from SrBG, which promoted mature bone formation in bone defects to a greater extent. Therefore, IFN-γ/SrBG scaffolds are expected to become excellent bone tissue engineering materials by sequential regulation of macrophage polarization.
研究领域:
生物材料
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组织工程
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免疫学
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骨科
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DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Xianghui Huang,Jia Xu,Ye Xu,Bingxin Huangfu,Feng Zhang,Yanzhou Hu,Ruxin Gao,Xinxin Ren,Boyang Zhang,Kunlun Huang,Xiaoyun He
Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health. However, to date, no approved therapeutic drugs have been developed. Dietary interventions with natural products have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompound with antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN can ameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying these beneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipid accumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis (NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line and the liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type and the regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophage M2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovered a new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFN might be protective against NASH.
研究领域:
肝病学
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免疫学
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药理学
·
营养学
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产品关联
DOI
高影响因子
Food & Function
·
2018
·Vol. 9
·期 11
·5547-5559
·
IF 3.289
Peng Yang,Guo-Bin Ding,Wen Liu,Rong Fu,Amin Sajid,Zhuoyu Li
Tannic acid (TA), a naturally occurring polyphenolic acid that is primarily found in grapes and green tea, exhibits potent antioxidant and anticarcinogenic characteristics. However, the underlying molecular mechanisms and targets of TA, which are responsible for cancer prevention, remain elusive. In the present study, we used TA-functionalized magnetite nanoparticles to identify pyruvate kinase isoenzyme M2 (PKM2) as the direct target of TA. We report that TA selectively inhibits the pyruvate kinase activity of PKM2, rather than protein kinase activity and PKM2 expression, to suppress colorectal cancer (CRC) cell proliferation. Furthermore, we had discovered that lysine residue 433 (K433) is a selective druggable site. Through direct binding to lysine residue 433, TA triggers the dissociation of PKM2 tetramers and further blocks the metabolic activity of PKM2. Notably, TA has no effect on PKM1 activity as TA does not bind to it. Taken together, these findings show that TA is worthy of consideration as a promising PKM2 inhibitor for the prevention of CRC.
研究领域:
肿瘤学
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分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Stroke & Cerebrovascular Diseases
·
2021
·
IF 2.136
Zhiyu Xi,Canxin Xu,Xiao Chen,Baofeng Wang,Zhihong Zhong,Qingfang Sun,Yuhao Sun,Liuguan Bian
Objectives Microglia activation, a key process in secondary injury following intracerebral hemorrhage (ICH), is divided to M1 and M2 phenotype. Protocatechuic acid (PCA) is a phenolic acid been proved neuroprotection in ICH without understanding of details. Thus, this study aimed to observe the influence of PCA on microglia activation and explore underlying mechanisms. Materials and methods To assess PCA affected microglia activation in vivo, an experimental ICH mice model was established and then treated with PCA intraperitoneal injection . Immunofluorescence staining was performed in brain slices at day 3 post ICH. BV2 cells were stimulated with hemin for activation, then M1 and M2 biomarkers were analyzed using Western Blot and qPCR. At last, we detected the expression of mTOR and its downstream molecules to discuss possible mechanisms. Results At day 3 post ICH, less activated microglia gathering around hematoma after PCA treatment . Furtherly, in hemin treated BV2 cells, PCA downregulated M1 and promoted M2 biomarkers expression in both mRNA and protein level. PCA inhibited the phosphorylation of mTOR, S6K1 and 4E-BP1, while the inhibition was disappeared after supplemented with mTOR activator. Conclusions PCA impacted microglia activation by suppressing the mTOR signaling pathway , thereby improving M1/M2 switch and attenuated neuroinflammation .
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
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2021
·
IF 3.046
Hui Tian,Yahong Cheng,Yiyuan Zhang,Xinying Bai,Yuan Jiang,Jinjin Li,Shiqi Fan,Hong Ding
This research aimed to examine the nutritious supplementary function of 18β-Glycyrrhetinic acid (18β-GA) in moderating the myelin sheath destruction and behavioral impairments observed in the cuprizone model of demyelination. Mice were fed daily on food containing cuprizone (0.3 %) and given doses of 18β-GA (5 or 1 mg/kg) for a period of five weeks. The groups treated with 18β-GA exhibited improvements in exploratory behavior, locomotive activity, and weight. As assessed using luxol-fast blue and myelin basic protein (MBP) staining, which were used to detect demyelination in the brain, 18β-GA both reduced and prevented instances of cuprizone-induced demyelinating lesions; treatment with 18β-GA also caused the MBP level in the corpus callosum to increase. Furthermore, alongside these positive results following 18β-GA treatment, microglial polarisation was also observed to shift towards the beneficial M2 phenotype. The results of this research thus indicate the potential clinical application of 18β-GA for the prevention of myelin damage and behavioral dysfunction.
研究领域:
神经科学
·
药理学
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免疫学
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DOI
高影响因子
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