ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Donglin Cai,Zhelun Li,Wendong Gao,Yuqing Mu,Jiaying Liu,Yufeng Zhang,Xiaohan Mei,Jingjing Quan,Lan Xiao,Yin Xiao
The temporary transition of macrophages from a pro-inflammatory macrophages (M1) to an anti-inflammatory macrophages (M2) is crucial for tissue repair and regeneration processes. Selectively targeting M1 macrophages is preferred to modulate inflammatory responses. However, macrophage populations are inherently heterogeneous, and the competitive phagocytosis of nanoparticles (NPs) by these two subtypes has not been thoroughly investigated. This study establishes a 3D cell co-culture system to evaluate the competitive phagocytosis of M1-targeting NPs under dynamic fluidic flow conditions. Bacterial outer membrane vesicles (OMVs) are utilized as a “trojan horse” to decorate gold nanocage (AuNC), creating hybrid NPs (AuNC-OM) capable of selectively targeting M1 macrophages. It is noted that the selective uptake of AuNC-OM by M1 macrophages is mediated through phagocytosis-related receptors CD64 and CD14, which are highly expressed on the M1 macrophage surfaces. Furthermore, the study demonstrates that AuNC-OM selectively targets M1 macrophages without affecting the phagocytosis of M2 macrophages. Once internalized, the nanoparticles release anti-inflammatory drugs, effectively reversing the inflammation. The release of dexmedetomidine from AuNC-OM protects against lipopolysaccharide (LPS)-induced bone resorption in a mouse model. This study presents a novel system for accurately assessing the M1 macrophage-targeting capabilities and introduces an innovative strategy for M1 macrophage-targeted therapy.
研究领域:
免疫学
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纳米医学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Rui Deng,Jibin Wu,Baokang Zhu,Gaoqing Song,Tao Zhou,Musheng Yang,Lingling Pan,Jian Wang,Xuan Zou,Ziquan Lv,Xiaobao Jin,Yinghua Xu,Xuemei Lu,Shuiqing Gui
Hepatocellular carcinoma (HCC) has emerged as one of the most prevalent and highly malignant tumor malignancies worldwide and is characterized by poor prognosis and high mortality. Therefore, effective medications are urgently needed to improve therapeutic effects with HCC. Exosomes are nanoscale vesicles that can transfer cellular information. Owing to their excellent biocompatibility, exosomes are frequently utilized as drug carriers for cancer treatment. Targeted drug delivery systems that modify exosomes to increase targeting have emerged as promising therapeutic platforms in response to the lack of precise targeting by natural exosomes. In this study, HTPP-Exo was successfully constructed by modifying the exosome membrane by connecting sulfhydryl group of HTPP with maleimide in DSPE-PEG2000-Mal, and the antimicrobial peptide M1–8 was included for the first time through co-incubation, thus successfully establishing the HTPP-Exo-M1–8 targeted drug delivery system. The targeting ability of HTPP-Exo-M1–8 was verified by evaluating its in vitro and in vivo targeting of HepG2 cells, and its therapeutic ability was evaluated by its inhibitory effect on HepG2 cells and in situ liver cancer in mice. The results showed that HTPP-Exo-M1–8 targeted drug delivery system could target HepG2 cells in vivo and in vitro , and the survival rate of HepG2 cells was 45 % after HTPP-Exo-M1–8 treatment for 48 h. After in vivo treatment, the volume of HCC in HTPP-Exo-M1–8 group (270.4 mm 3 ) was much smaller than that in control group (969.5 mm 3 ), which achieved the expected purpose of HCC treatment. Further research showed that the targeted drug delivery system HTPP-Exo-M1–8 could be used to treat HCC by inhibiting the lysosome–autophagosome fusion in HepG2 cells. Additionally, there was no obvious toxicity to healthy cells or tissues when HTPP-Exo-M1–8 was used. Overall, the exosome-based targeted drug delivery system HTPP-Exo-M1–8 can treat HCC by targeting and penetrating tumor cells, which provides a new strategy for the treatment of HCC.
研究领域:
肿瘤学
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药学
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生物技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2025
·
IF 3.8
Shu Wang,Ye Gong,Yang Ji,Dandan Liu,Hao Pan,Weisan Pan
By inducing apoptosis, promoting differentiation and reducing the migration of cancer cells, arsenic has a higher therapeutic effect and lower risk of recurrence and metastasis than conventional anticancer drugs. However, the low bioavailability and adverse side effects of arsenic hinder its application in hepatocellular carcinoma (HCC). Therefore, a M1 macrophage membrane-coated nickel-arsenic/polydopamine nanocomplex (NiAsOx@P@M) was constructed to enhance the combined antitumor effects of chemotherapy and immunotherapy. The nanocomplex consisted of a nickel-arsenic oxide core, a polydopamine (PDA) shell and a M1 macrophage membrane (MM) coating. MM endowed the nanocomplex with natural tumor homing and immune escape properties, and the nanocomplex was gradually accumulated in the tumor tissue during the internal circulation. The acid response of PDA led to its degradation in the tumor microenvironment (TME). The degradation product dopamine (DA) and MM jointly promoted tumor immunity and regulated tumor-associated macrophages (TAMs) to repolarization M1 phenotype. The nickel-arsenic oxide core dissociated in an acid environment and released arsenic, thus killing tumor cells. In summary, the nanocomplex provided a promising delivery strategy for arsenic therapy of HCC and a novel design idea for the conversion of inorganic drugs into organic preparations.
研究领域:
肿瘤学
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药剂学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
·
2023
·
IF 3.5
Honglin Li,Congcong Du,Ting Guo,Hongyuan Zhou,Ying Zhou,Xinrui Huang,Yu Hao Zhang,Shuo Wang,Xiaozhu Liu,Liang Ma
ABSTRACT A novel ratiometric electrochemical aptasensor based on split aptamer and Au-rGO nanomaterials was proposed to detect Aflatoxin M1 (AFM1). In this work, Au-rGO nanomaterials were coated on the electrode through the electrodeposition method to increase the aptamer enrichment. We split the aptamer of AFM1 into 2 sequences (S1 and S2), where sequence S1 was immobilized on the electrode due to the Au-S bond, whereas sequence S2 was tagged with methylene blue (MB) and acted as a response signal. A complementary strand to S1 (CS1) labeled with ferrocene (Fc) was introduced as another reporter. In the presence of AFM1, CS1 was released from the electrode surface due to the formation of the S1-AFM1-S2 complex, leading to a decrease in Fc and an increase in MB signal. The developed ratiometric aptasensor exhibited a linear range of 0.03 μg L −1 to 2.00 μg L −1 , with a detection limit of 0.015 μg L −1 for AFM1 detection. The ratiometric aptasensor also showed a linear relationship from 0.2 μg L −1 to 1.00 μg L −1 , with a detection limit of 0.05 μg L −1 in natural milk after sample pretreatment, indicating the successful application of the developed ratiometric aptasensor. Our proposed strategy provides a new way to construct aptasensors with high sensitivity and selectivity.
研究领域:
生物传感技术
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食品安全检测
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纳米材料应用
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PERIODONTAL RESEARCH
·
2025
·
IF 3.4
Jiaying Song,Xingyi Li,Kailibinuer Abuduwaili,Yue Sun,Jiangbo Li,Danying Chen,Zhuofan Chen,Zhipeng Li,Baoxin Huang
Aim Periodontitis is a chronic inflammatory disease initiated by dysbiosis of the local microbial community. As a non-specific phosphodiesterase inhibitor, dipyridamole features anti-oxidant and anti-inflammatory properties. This study aimed to investigate the effects of dipyridamole in an experimental rat model of periodontitis. Methods Thirty rats were divided randomly into three groups ( n = 10): non-ligature group (NL), ligature-induced periodontitis group (L), and ligature-induced periodontitis with dipyridamole administered group (L + D). All rats were euthanized on Day 14. Alveolar bone resorption was analyzed by microcomputed tomography. The mRNA levels of Il1b , Il6 , tumor necrosis factor alpha ( Tnfa ), and inducible nitric oxide synthase ( iNos ) in gingival tissue were assessed by real-time quantitative polymerase chain reaction (qRT-PCR). Inflammation level, osteoclasts, and macrophages infiltration were analyzed histologically. RAW264.7 macrophages were stimulated with Porphyromonas gingivalis lipopolysaccharide ( P.g. LPS) to induce M1 polarization. Different concentration of dipyridamole (0/2/10 μM) was added simultaneously. To explore the role of PKA/PKG pathways, RAW 264.7 macrophages were pretreated with 10 μM H-89 (PKA inhibitor) or 1 μM KT-5823 (PKG inhibitor), respectively. Expression of pro-inflammatory cytokines and M1 markers were detected by qRT-PCR, ELISA, and flow cytometry. Results Dipyridamole administration reduced alveolar bone loss, protein levels of inflammatory cytokines, and osteoclastogenesis in rats with experimental periodontitis. It also showed a tendency to decrease mRNA levels of Il1b , Il6 , and Tnfa but without significant differences in gingival tissues. Moreover, the infiltration of macrophage and M1 macrophage polarization in gingival tissue of periodontitis rats were inhibited by dipyridamole administration. In addition, dipyridamole could downregulate the gene expression of Il1b and Tnfa , as well as the protein level of TNF-α, CD86, and iNOS in RAW264.7 treated with P.g. LPS. When PKA/PKG pathways were blocked, the suppression of TNF-α, CD86, and iNOS was reversed significantly. Conclusion Dipyridamole alleviated experimental periodontitis in rat models by regulating M1 polarization via activation of PKA/PKG pathways and emerges as a hopeful remedy for periodontitis. Graphical As non-specific phosphodiesterase inhibitor, dipyridamole reduced alveolar bone loss, expression level of inflammatory cytokines, and osteoclast genesis in ligature-induced periodontitis of rats by regulating M1 macrophage polarization via activation of PKA/PKG pathways, emerging as a hopeful treatment for periodontal disease.
研究领域:
牙医学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Liang Pang,Ying Zhu,Jing Qin,Wenjie Zhao,Jianxin Wang
Glioma remains difficult to treat because of the infiltrative growth of tumor cells and their resistance to standard therapy. Despite rapid development of targeted drug delivery system, the current therapeutic efficacy is still challenging. Based on our previous studies, macrophages have been proved to be promising drug carrier for active glioma delivery. To make full use of macrophage carrier, primary M1 macrophages were proposed to replace regular macrophage to deliver nanodrugs into glioma, because M1 macrophages not only have the natural ability to home into tumor tissues, but they also have stronger phagocytic capability than other types of macrophage, which can enable them to uptake enough drug-loaded nanoparticles for therapy. In addition, M1 macrophages are not easily affected by harsh tumor microenvironment and inhibit tumor growth themselves. In this study, M1 macrophage-loaded nanoparticles (M1-NPs) were prepared by incubating poly(lactide-co-glycolide) (PLGA) nanoparticles with primary M1 macrophages. In vitro cell assays demonstrated M1 macrophage still maintained good tumor tropism capability after particle loading, and could efficiently carry particles across endothelial barrier into tumor tissues. In vivo imaging verified that M1-NPs exhibited higher brain tumor distribution than free nanoparticles. DOX@M1-NPs (doxorubicin-loaded M1-NPs) presented significantly enhanced anti-glioma effect with prolonged survival median and increased cell apoptosis. In conclusion, the results provided a new strategy exploiting M1 macrophage as carrier for drug delivery, which improved targeting efficiency and therapeutic efficacy of chemodrugs for glioma therapy.
研究领域:
药理学
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肿瘤学
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纳米医学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2022
·
IF 11.6
Liling Wang,Huan Wang,Jing Luo,Ting Xie,Gil Mor,Aihua Liao
Rationale: Recurrent pregnancy loss (RPL) is a distressing disorder that seriously affects the physical and psychological health of women. RPL is also a sentinel risk marker for future obstetric complications and warrants in-depth investigation. Abnormal polarization and functions of decidual macrophages are associated with RPL; however, the underlying mechanisms remain poorly understood. Methods: Decorin expression, localization, and content in the decidua of women with normal pregnancy (NP) and those with RPL were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, immunofluorescence, and enzyme-linked immunosorbent assay. The profiles of decidual macrophage subsets were determined using flow cytometry and immunofluorescence in both groups. The correlation between decorin content and the proportion of decidual macrophage subsets in the decidua of early NP women was determined using Pearson analysis. The effects of decorin on the polarization and functions of macrophages were assessed in an in-vitro model of Raw264.7 cells via flow cytometry, western blotting, and RT-qPCR. Moreover, the mitochondrial metabolism in Raw264.7 cells under decorin administration was measured via flow cytometry, western blotting, and immunofluorescence. Thirty-three pregnant mice were included in the in vivo model and underwent different treatments. The embryo abortion rate, macrophage phenotype in the spleen and uteri, and placental development were evaluated using flow cytometry and hematoxylin-eosin staining. Results: Decorin, derived from decidual stromal cells, was highly expressed in the decidua of women with RPL. A positive correlation between decorin content and the proportion of M1-like macrophages was also observed in the decidua of early NP women. In vitro studies showed that decorin treatment inhibited macrophage polarization to M2-like subsets and boosted the inflammatory response, which was related to enhanced anaerobic glycolysis, increased mitochondrial membrane potential and intracellular reactive oxygen species levels, reduced mitochondrial mass, and activation of the myeloid differentiation primary response 88-nuclear factor-κB signaling pathway. Adoptive transfer of decorin-treated bone marrow-derived macrophages in pregnant C57BL/6 mice increased the embryo absorption, accompanied by impaired fetal vascularization. Conclusions: Decidual stromal cell-derived decorin can polarize decidual macrophages toward the M1 phenotype by regulating mitochondrial metabolism, resulting in the occurrence of RPL.
研究领域:
妇产科学
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免疫学
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细胞生物学
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生殖医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-13
·
IF 3.8
Zhu Dongsheng,Chen Feng,Qiang Hongjia,Qi Han
To clarify the impact of SETD2 on macrophage function in pediatric patients with acute suppurative osteomyelitis and to elucidate the precise underlying mechanism. To gain insights into the potential functions of SETD2, a comprehensive study was conducted utilizing a co-culture model of human bone mesenchymal stem cells (hBMSCs) and bone marrow-derived macrophages (THP-1). A range of techniques were employed, including quantitative polymerase chain reaction, western blotting, ELISA, alkaline phosphatase activity assays, alizarin red S staining, luciferase reporter gene assays, and chromatin immunoprecipitation, to unravel the intricate interactions and molecular mechanisms involving SETD2 in this system. It was observed that SETD2 expression was reduced in THP-1 cells stimulated by staphylococcal protein A (SPA). Furthermore, the downregulation of SETD2 resulted in elevated M1 macrophage polarization and glycolysis, effects that were mitigated by SPA stimulation. Notably, SPA-stimulated THP-1 cells exhibited an increase in HIF-1α expression, which exhibited an inverse correlation with SETD2 levels. Moreover, it was discovered that SETD2 functioned as a catalyst for H3K36me3 and bound to the HIF-1α gene, which, in turn, regulated HIF-1α expression. Furthermore, the suppression of HIF-1α abrogated the consequences of SETD2 downregulation on glycolysis and M1 macrophage polarization. Lastly, the study demonstrated that M1 macrophage polarization serves as a mediator for BMP4’s inhibitory effect on osteogenic differentiation of hBMSCs. This research has uncovered a previously unknown role of SETD2 in macrophages during osteomyelitis, revealing its significance in the pathogenesis of this condition. These findings suggest SETD2 as a novel target for the treatment of osteomyelitis.
研究领域:
免疫学
·
分子生物学
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细胞生物学
·
骨科
✓ 已验证
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
·
组织工程
·
免疫学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Biology
·
2025
·
IF 2.6
Xi-Ting Lv,Wen-Xiu Yang,Xiao Zhang,Bao-Ling Li,Wen-Ying Wang,Guo-En Wang
Guilongwan (GLW), a representative of traditional Chinese Medicine (TCM) has been utilized to treating diabetic foot ulcer (DFU)-related syndrome including an intolerance of cold with cold limbs, blood circulation disorder, and immune dysfunction for decades. However, the chemical and biological mechanisms of GLW remain unclear. This study aims to discover the biological mechanisms of GLW on DFU by using streptozotocin- and skin-puncher-induced DFU rat models, in vitro macrophage models, and in silico analysis. The alterations in pathology, Notch1 signaling, and macrophage polarization are detected. The results indicated that GLW promoted wound healing, cutaneous cell proliferation, and angiogenesis in DFU rats by inhibiting delta-like (DLL) 4/Notch1 signaling. In addition, GLW inhibited M1 polarization and promoted M2 polarization in diabetic wounds. Seventeen chemical compounds in GLW-medicated serum are identified. In silico analysis and in vitro experiments demonstrated that GLW-medicated serum and its main compounds inhibited the expression of DLL4 in matrix metalloproteinase-9-induced M1 macrophages. In conclusion, GLW ameliorated experimental DFU rats via the inhibition of DLL4/Notch1 signaling in M1 macrophages. This study provided a new biologic mechanism for GLW in the treatment of DFU.
研究领域:
药理学
·
分子生物学
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中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Ru-Yang Zhao,Mu-Zi Li,Qi-Qian Wang,Fu-Wei Jiang,Yi Zhao,Jin-Long Li
Butachlor (BTR), a globally prevalent amide herbicide, poses significant environmental health risks due to its bioaccumulation potential and documented chronic toxicity in mammalian systems. Given the spleen's pivotal role in orchestrating systemic immune homeostasis, this study investigated BTR-induced immunopathological mechanisms in ICR mice following 28-day subacute exposure (10 mg/kg). Histopathological examination revealed significant disorganization of the splenic marginal zone architecture, concomitant with ultrastructural mitochondrial abnormalities and a reduction in mitochondrial membrane potential (ΔΨm). Mitochondrial permeability transition pore opening triggered cytoplasmic translocation of mitochondrial DNA (mtDNA), activating the stimulator of interferon genes (STING) pathway—a master regulator of innate immunity. STING activation initiated bifurcated downstream signaling, evidenced by TBK1 phosphorylation and subsequent IRF3 / NF-κB nuclear translocation. This dual signaling cascade simultaneously executed immunogenic cell death via Gasdermin D-dependent pyroptosis (cleaved GSDMD-NT) and drove macrophage polarization (IFN-α / β, IL-1β, TNF-α). Crucially, pharmacological STING inhibition with C-176 attenuated both pyroptosis (GSDMD cleavage reduced) and inflammatory cytokine surge. Our findings not only pioneer the identification of the mtDNA-STING axis as the central mechanism underlying BTR-induced splenic immunotoxicity but also validate STING inactivation as a targeted strategy to mitigate herbicide-associated immune dysfunction. This work provides critical insights for environmental toxicant risk assessment and immunomodulatory.
研究领域:
环境毒理学
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免疫学
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分子生物学
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药理学
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细胞生物学
✓ 已验证
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
·
药理学
·
分子生物学
✓ 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）