International Journal of Nanomedicine
·
2025
·
IF 6.5
Ren Na,Jianmei Jing,Hua Yang,Ye Li,Xiaofeng Yuan,Xue Sun,Jiangfan Han,Jiajun Wang,Zhenhua Tong,Guangbin He,Weiliang Ye
Objective Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) but has poor targeting and significant side effects. This study developed MTX-loaded lipid nanoparticles modified with PVCAM-1 peptide (MTX@LNP-PVCAM-1) to enhance targeting and reduce toxicity.Methods MTX@LNP-PVCAM-1 was prepared using the thin-film dispersion method. Particle size and morphology were assessed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Biocompatibility was tested using human umbilical vein endothelial cells (HUVEC) and hemolysis assays. Cellular uptake was examined via fluorescence microscopy, while cytotoxicity and cell migration inhibition were evaluated using CCK-8 and scratch assays. Inflammatory cytokines (IL-1β, IL-6) were measured by ELISA. Distribution in adjuvant-induced arthritis (AIA) rats was observed using in vivo imaging, and safety and anti-inflammatory effects were assessed through blood tests, paw volume, joint scores, and histology.Results MTX@LNP-PVCAM-1 had an average particle size of 168.5 nm, PDI of 0.142, and zeta potential of −12.1 mV, with spherical morphology. It exhibited pH responsiveness and good biocompatibility. Compared with unmodified MTX@LNP, PVCAM-1 surface modification significantly increased cellular uptake efficiency (p<0.05) and more effectively inhibited the growth (p<0.05), migration (p<0.05), and secretion of inflammatory cytokines (significantly reduced levels of IL-1β and IL-6, p<0.05) of synovial fibroblasts. In animal experiments, the accumulation of MTX@LNP-PVCAM-1 in inflamed sites was significantly higher than that of MTX@LNP (p<0.05), demonstrating good targeting. Moreover, it enhanced the anti-inflammatory effects of methotrexate in AIA rats, significantly reducing paw swelling (p<0.05) and joint clinical scores (p<0.05). Importantly, it had no significant effect on the blood routine indicators of rats (p>0.05), indicating no obvious toxicity.Conclusion MTX@LNP-PVCAM-1 combines passive and active targeting, delivering MTX efficiently to inflamed sites and reducing toxicity. This approach enhances anti-inflammatory effects in AIA rats, offering a potential strategy for low-toxicity RA treatment.
研究领域:
纳米医学
·
风湿病学
·
药物递送
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炎症性疾病
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生物药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2014
·
IF 5.71
Simin Yan,Xu Zhang,Haili Zheng,Danhong Hu,Yongtian Zhang,Qinghua Guan,Lifang Liu,Qilong Ding,Yunman Li
Proinflammatory cytokine TNF-α-induced adhesion of leukocytes to endothelial cells plays a critical role in the early stage of atherosclerosis . Oxidative stress and redox-sensitive transcription factors are implicated in the process. Thus, compounds that mediate intracellular redox status and regulate transcription factors are of great therapeutic interest. Clematichinenoside (AR), a triterpene saponin isolated from the root of Clematis chinensis Osbeck , was previously demonstrated to have anti-inflammatory and antioxidative properties. However, little is known about the exact mechanism underlying these actions. Thus we performed a detailed study on its effect on leukocytes–endothelial cells adhesion with TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) and cell-free systems. First, we found that AR reduced TNF-α-induced VCAM-1 and ICAM-1 expression and their promoter activity, inhibited translocation of p65 and phosphorylation of IκBα , suppressed IκB kinase-β (IKK-β) activity, lowered O 2 ∙− and H 2 O 2 levels, tackled p47 phox translocation, and decreased NOX4 NADPH oxidase expression. Second, we showed that AR exhibited no direct free radical scavenging ability in cell-free systems at concentrations that were used in intact cells. Besides, AR had no direct effect on the activity of IKK-β that was extracted from TNF-α-stimulated HUVECs. We also found that p47 translocation, NOX4 expression, and reactive oxygen species (ROS) levels were up-regulated before IκB phosphorylation in TNF-α-induced HUVECs. Moreover, TNF-α-enhanced IKK-β activity was also inhibited by (polyethylene glycol) PEG–catalase, N -acetylcysteine (NAC), and vitamin E. In conclusion, these results suggest that AR reduces VCAM-1 and ICAM-1 expression through NADPH oxidase-dependent IKK/NF-κB pathways in TNF-α-induced HUVECs, which finally suppress monocyte–HUVECs adhesion. This compound is potentially beneficial for early-stage atherosclerosis.
研究领域:
药理学
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免疫学
·
心血管研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Yuanyuan Wang,Ruibo Guo,Baoli Xu,Ming Zou,Liang Kong,Chuan Tang,Runchao Jiang,Wei Wang,Xuan Zhang,Guangyao Lv
Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent synovitis and the formation of pannus, leading to proliferation of synovial tissue and destruction of bone and cartilage. Traditional drug therapy is often limited by the lack of drug targeting and the continuous synovial angiogenesis. Herein, a dual-targeted micelles for macrophages and vascular endothelial cells with excellent anti-inflammatory and anti-angiogenic properties was constructed to effectively treat RA. Methods: We developed vascular cell adhesion molecule-1 (VCAM-1) binding peptide modified polyphyllin I (PPI) loaded micelles (VM-PE@Ms) in which eucommia ulmoides polysaccharide (EUP) was used as the hydrophilic parts of the hybrid micelles. The targeting, ROS scavenging effect, anti-inflammatory activity, and inhibition of angiogenesis of the micelles were assessed in vitro. Collagen-induced arthritis (CIA) rats model was employed to explore targeting, impact on inflammatory cytokine levels, and cartilage protective effect of the micelles in vivo. Results: VM-PE@Ms. exhibited targeting to both activated RAW264.7 cells and human umbilical vein endothelial cells (HUVECs), and strong inhibitory effect of inflammatory cytokine secretion, ROS generation, and angiogenesis. In vivo assays demonstrated that VM-PE@Ms. displayed desirable pharmacodynamics property, which was confirmed by precise inflammatory joint targeting and retention capacity and bone erosion remission effects and was related to suppression of inflammation and synovial angiogenesis. Conclusion: In summary, the proposed dual-targeted hybrid micelles have the potential role for anti-inflammatory and anti-angiogenic therapy of RA.
研究领域:
纳米医学
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风湿病学
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药物递送
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炎症
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血管生成
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 5
·1379
·
IF 5.4
Yongyu Tang,Ying Chen,Qianqian Guo,Lidan Zhang,Huanhuan Liu,Sibu Wang,Xingjie Wu,Xiangchun Shen,Ling Tao
Due to the accompaniment of vascular endothelial inflammation during the occurrence and development of cardiovascular diseases (CVD), treatment modalities against vascular endothelial inflammation have been intensively investigated for CVD prevention and/or treatment. Vascular cell adhesion molecule-1 (VCAM-1) is a typical transmembrane inflammatory protein specifically expressed by inflammatory vascular endothelial. By inhibiting VCAM-1 expression through the miR-126 mediated pathway, vascular endothelial inflammation can be efficiently relieved. Inspired by this, we developed a miR-126-loaded immunoliposome with VCAM-1 monoclonal antibody (VCAMab) decorated at its surface. This immunoliposome can be directly targeted to VCAM-1 at the inflammatory vascular endothelial membrane surface and achieve highly efficient treatment against inflammation response. The cellular experiment results showed the immunoliposome had a higher uptake rate towards inflammatory human vein endothelial cells (HUVECs) and can significantly downregulate the VCAM-1 expression level of inflammatory HUVECs. In vivo investigation further demonstrated that this immunoliposome displayed a higher accumulation rate at vascular inflammatory dysfunction sites than its non-VCAMab-modified counterpart. These results suggest that this novel nanoplatform can effectively deliver miR-126 to vascular inflammatory endothelium, opening a new avenue for the safe and effective delivery of miRNA for potential clinical application.Keywords:vascular endothelial inflammation treatment;miR-126 delivery;VCAM-1 targeting;cationic liposomes
研究领域:
心血管疾病
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纳米技术
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分子生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yuan Zhong,Xian Qin,Yi Wang,Kai Qu,Li Luo,Kun Zhang,Boyan Liu,Essam Abdo Mohammed Saad Obaid,Wei Wu,Guixue Wang
For atherosclerosis (AS) management, a therapeutic drug intervention is the most widely used strategy. However, there are some problems such as low location specificity, high intake, and side effects. Nanomedicine can prolong the half-life of drug solubilization, reduce toxic and side effects, and improve the distribution of drug objects. Herein, to overcome the challenges, an erythrocyte-based “plug and play” nanoplatform was developed by incorporating the vascular cell adhesion molecule-1 (VCAM-1) targeting and the acid stimulus responsibility. After the function moieties conjugated with DSPE-PEG, the targeting peptide and the acid-sensitive prodrug were conveniently integrated into red blood cells’ surface for enhancing target AS drug delivery and controlling local drug release. As a proof of principle, a plug and play nanoplatform with targeted drug delivery and acid-control drug release is demonstrated, achieving a marked therapeutic effect for AS.
研究领域:
药学
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Lan Tian,Duan Guozhen,Qi Youchao,Almezgagi Maged,Fan Guanghui,Ma Yonggui
Wolfberry, esteemed as a traditional Chinese medicinal material and functional food, is replete with nutrients and boasts a diverse array of health benefits, including hypoglycemic, antitumor, antioxidant, anti-inflammatory, and immune-enhancing properties. Notably, inflammation is a pivotal factor in the onset and progression of numerous diseases. Despite this, there is a paucity of research on the comprehensive evaluation of the components found in different wolfberries, and the exploration of their primary active components is limited. To address this issue, we conducted a comprehensive targeted metabolomics analysis, employing statistical methods such as principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), KEGG pathway analysis, and volcano plots to delineate the compositional differences among red, black, and yellow wolfberries. Furthermore, we investigated the anti-inflammatory effects of their primary components through in vitro experiments. Our analysis revealed a total of 1,104 chemical compositions in the three wolfberries, with alkaloids, phenolic acids, flavonoids, and lipids being the predominant nutritional components. KEGG enrichment analysis indicated that these compositions were primarily involved in the biosynthesis of secondary metabolites, ABC transport, and galactose metabolism pathway. Moreover, our study demonstrated that quercetin exhibited dose-dependent anti-inflammatory activity in LPS-stimulated HUVECs. It effectively inhibited the production of inflammatory factors such as TNF-α, MCP-1, and IL-1β, while also down-regulating the gene and protein expression levels of ICAM-1 and VCAM-1. In conclusion, our findings indicate that there are variations in compositions among the three wolfberries, with flavonoids being the most abundant, and in vitro studies also confirmed the anti-inflammatory potential of quercetin. It is worth noting that Lycium ruthenicum contains higher levels of antioxidant components and possesses greater nutritional value, providing valuable insights for the future development and utilization of the three wolfberries.
研究领域:
药理学
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代谢组学
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生物化学
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药物化学
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植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yuan Zhong,Kai Qu,Wenhua Yan,Kun Zhang,Xian Qin,Yi Wang,Meng Yan,Shuai Wu,Li Zhu,Essam Abdo Mohammed Saad Obaid,Guixue Wang,Wei Wu
The development of atherosclerosis (AS) is closely related to inflammation. The common feature of inflammatory sites is upregulation of vascular cell adhesion molecule-1 (VCAM-1), which has a strong affinity with very late antigen-4 (VLA-4). Endothelial cell membranes overexpressing VLA-4 (OEM) were used to camouflage rapamycin nanoparticles (RAP NPs) with reactive oxygen species (ROS) responsiveness to construct biomimetic nanodrugs [email protected] NPs. These nanoparticles were capable of enhancing the active target drug delivery and ROS-responsive drug release under the pathological overexpression of VCAM-1 and accumulation of ROS stimulus. In vitro and in vivo investigations confirmed that [email protected] NPs could enhance the active target drug delivery to atherosclerotic plaques and increase drug accumulation in the focal site, thus improving the bioavailability of drugs, reducing side effects and inhibiting the occurrence and development of atherosclerosis.
研究领域:
药理学
·
纳米技术
·
心血管疾病
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 23
·12844
·
IF 4.9
Zhining Gao,Haoyang Dai,Qinqin Zhang,Fan Yang,Chenxi Bu,Suiqing Chen
Acute liver injury (ALI) is an injury to liver tissue caused by viruses, drugs, alcohol, and oxygen deprivation, and is one of the most common and serious clinical disorders. Hydroxytyrosol (HT) is a naturally occurring polyphenolic compound isolated from forsythia and has excellent anti-inflammatory properties. However, the effect and mechanisms of HT in ALI remain unclear. We used the LPS/D-GalN induced experimental ALI mouse model and AML12 cells to reveal the efficacy and potential mechanisms of HT in ALI, and HE staining was used for the evaluation of pathologies. A biochemical assay was used to detect changes in liver function, RNA-seq was conducted to reveal the underlying mechanisms of HT for ALI, and WB, RT-qPCR, and IF were used to assess the effects of HT action. Furthermore, an in vitro ALI model against HT in AML12 cells induced by LPS/D-GalN was used to assess the HT protection mechanism. HT significant alleviated LPS/D-GalN-induced ALI in the mice by suppressing inflammatory. In terms of RNA-seq, HT improved the TNF, ECM-receptor interaction, and PI3K/AKT signaling pathway, and it downregulated the mRNA levels of VCAM-1, CXCL5, TNF-α and IL-6 in the liver. Mechanically, HT alleviated LPS/D-GalN in the mice by targeting TNF-α, thereby inhibiting the TNF-α/PI3K/AKT signaling pathway.
研究领域:
药理学
·
肝病学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2019
·
IF 3.532
Juan-Fang Lin,Lu-Lu Fan,Bo-Wen Li,Rui-Rui Zhao,Long-Guang Jiang,Bing-Chen Zhang,Yu-Sheng Lu,Jing-Wei Shao
Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases. However, the clinical safety and effectiveness of herb-drug combination treatment are still controversial. Therefore, it is very essential to probe the interaction between warfarin and ginseng. In this study, in vitro and in vivo study was carried out to demonstrate that whether there is an interaction between warfarin and ginsenosides (GS), which is the main component of ginseng. In vitro study showed that the adhesion ability between endothelial cells and matrigel/platelets was enhanced due to the up-regulating expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins by treatment of warfarin+GS combination compared to warfarin/GS treatment alone. Moreover, GS could weaken the anticoagulation effect of warfarin in hyperlipemia rats owning to the increased expression levels of coagulation factors and hepatic cytochrome P450 enzymes in plasma after long-term co-administration of warfarin with GS. The results of both in vitro and in vivo study demonstrated that there is a serious interaction between warfarin and ginseng, which may deteriorate atherosclerosis and thrombosis after combined use of warfarin and GS.
研究领域:
药理学
·
心血管疾病
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2016
·Vol. 38
·期 6
·1871-1878
·
IF 2.348
Xusheng Yuan,Junjun Chen,Min Dai
Paeonol (2'-hydroxy-4'-methoxyacetophenone) is an active component isolated from the root of Paeonia Suffruticosa Andrews. We previously found that paeonol inhibited vascular cell adhesion molecule-1 (VCAM‑1) expression, and thus may be useful for the prevention and treatment of rabbit atherosclerosis (AS); however, the underlying mechanisms are not yet well known. Recently, microRNAs (miRNAs or miRs) have been reported to play an important role in the pathogenesis of AS. In the present study, we examined the effects of paeonol on miRNA-126 (miR‑126) expression, and its ability to inhibit monocyte adhesion to oxidized low-density lipoprotein (ox-LDL)-injured vascular endothelial cells (VECs). VECs were isolated from the rat thoracic aorta and stimulated with ox-LDL (20 mg/l) in the presence of paeonol. We found that miR‑126 had a lower expression in the ox-LDL-injured VECs, and VCAM‑1 was identified as a target gene of miR‑126. Furthermore, paeonol promoted miR‑126 expression and suppressed VCAM‑1 expression at the mRNA and protein level. It also inhibited monocyte adhesion to ox-LDL-injured VECs through the promotion of miR‑126 expression. Furthermore, it was demonstrated that paeonol blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway by promoting miR-126 expression. Taken together, and to the best of our knowledge, the findings of this study provide the first evidence that paeonol promotes miR‑126 expression to inhibit monocyte adhesion to ox-LDL-injured VECs and block the activation of the PI3K/Akt/NF-κB signaling pathway. Our data suggest that miR‑126 plays a crucial role in vascular inflammation and may be an important therapeutic target in the treatment of AS with the use of paeonol.
研究领域:
药理学
·
分子生物学
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Linghu Ke-Gang,Wu Guo-Ping,Fu Ling-Yun,Yang Hong,Li Hai-Zhi,Chen Yan,Yu Hua,Tao Ling,Shen Xiang-Chun
1,8-Cineole (eucalyptol), a monoterpene, has been widely reported for the anti-inflammatory effects. Our previous data confirmed that 1,8-cineole ameliorated the inflammatory phenotype of human umbilical vein endothelial cells (HUVECs) by mediating NF-κB expression in vitro. At present, we investigated the protection effects of 1,8-cineole on vascular endothelium in lipopolysaccharide (LPS)-induced acute inflammatory injury mice and the potential mechanisms involved in the protection in HUVECs. Results from enzyme linked immunosorbent assays revealed that 1,8-cineole suppressed the secretion of interleukin (IL)-6 and IL-8 and increased the expression of IL-10 in the serum of LPS-induced mice. 1,8-Cineole reduced the inflammatory infiltration and the expression of vascular cell adhesion molecular 1 (VCAM-1) in the sections of thoracic aorta in LPS-induced acute inflammatory mice. Western blotting indicated that 1,8-cineole significantly decreased the phosphorylation of NF-κB p65 and increased the expression of PPAR-γ in the thoracic aorta tissue. 1,8-Cineole increased the expression of PPAR-γ in LPS-induced HUVECs. 1,8-Cineole and rosiglitazone reduced the protein and mRNA levels of VCAM-1, E-selectin, IL-6, and IL-8 in LPS-induced HUVECs, which could be reversed by the action of GW9662 (inhibitor of PPAR-γ). 1,8-Cineole and rosiglitazone blocked the LPS-induced IκBα degradation and NF-κB p65 nucleus translocation, which could be reversed by the pretreatment of GW9662 or silence of PPAR-γ gene. In conclusion, 1,8-cineole attenuated LPS-induced vascular endothelial cells injury via PPAR-γ dependent modulation of NF-κB.
研究领域:
药理学
·
免疫学
·
分子生物学
·
心血管科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Zishuo Zhou,Yaxue Liu,Pei Xie,Zongning Yin
Atherosclerosis is a chronic multifactorial cardiovascular disease. To combat atherosclerosis effectively, it is necessary to develop precision and targeted therapy in the early stages of plaque formation. In this study, a simvastatin (SV)-containing prodrug micelle SPCPV was developed by incorporating a peroxalate ester bond (PO). SPCPV could specifically target VCAM-1 overexpressed at atherosclerotic lesions. SPCPV contains a carrier (CP) composed of cyclodextrin (CD) and polyethylene glycol (PEG). At the lesions, CP and SV exerted multifaceted anti-atherosclerotic effects. In vitro studies demonstrated that intracellular reactive oxygen species (ROS) could induce the release of SV from SPCPV. The uptake of SPCPV was higher in inflammatory cells than in normal cells. Furthermore, in vitro experiments showed that SPCPV effectively reduced ROS levels, possessed anti-inflammatory properties, inhibited foam cell formation, and promoted cholesterol efflux. In vivo studies using atherosclerotic rats showed that SPCPV reduced the thickness of the vascular wall and low-density lipoprotein (LDL). This study developed a drug delivery strategy that could target atherosclerotic plaques and treat atherosclerosis by integrating the carrier with SV. The findings demonstrated that SPCPV possessed high stability and safety and had great therapeutic potential for treating early-stage atherosclerosis.
研究领域:
药理学
·
心血管疾病
·
药物递送系统
·
纳米技术
✓ 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）