MATERIALS & DESIGN
·
2022
·
IF 9.417
Lingling Pan,Dawei Jiang,Luqi Pan,Zhizhen Meng,Yangyang Zhuang,Yueyue Huang,Fanrong Ye,Changcan Shi,Jie Chen,Jingye Pan
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and causes high ratios of morbidity and mortality worldwide. Although many potential therapeutic targets have been reported, the therapeutic effect needs to be further improved. Herein, we report a strategy to specifically target inflammation site via anti-ICAM-1 antibody bonded antibacterial peptides polymeric nanoparticle. Antibacterial peptide (KR-12) grafted amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 block copolymer and PCL- b -P(OEGMA- co -AMA)- g -biotin block copolymer were synthesized by ring-opening polymerization and click chemistry. Then, antibacterial peptides polymeric nanoparticles (AMPNP) were prepared by co-assembly of amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 and PCL- b -P(OEGMA- co -AMA)- g -biotin in aqueous solution. Intercellular adhesion molecule-1 (ICAM-1) is highly expressed on the surface of inflammatory endothelial cells, and the anti-ICAM-1 antibody can specifically bind to it. To obtain the anti-ICAM-1-AMPNP nanoparticles, biotinylated anti-ICAM-1 antibodies were bonded on the surface of AMPNP nanoparticles through the biotin-avidin system. The anti-ICAM-1-AMPNP nanoparticles had low systemic toxicity and exhibited ideal antibacterial property against drug-resistant bacteria, Gram-negative bacteria and Gram-positive bacteria. The anti-ICAM-1-AMPNP nanoparticles exhibited favorable targeting capabilities to inflammation endothelial cells in vitro and significantly reduced the inflammatory response of CLP mice in vivo . The present investigation might provide a specific strategy for targeting combating sepsis with anti-ICAM-1-AMPNP nanoparticles.
研究领域:
药学
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纳米技术
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感染病学
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免疫学
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高分子化学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Fei Tong,Suhuan Liu,Bing Yan,Xuejun Li,Shiwei Ruan,Shuyu Yang
The purpose of the study was to reveal the therapeutic effect of quercetin (QUE) nanoparticle complex on diabetic nephropathy (DN) by regulating the expression of intercellular adhesion molecular-1 (ICAM-1) on endothelium as compared to free QUE. QUE 10 mg/kg as a single abdominal subcutaneous injection daily for 8 weeks continuously in diabetic rats and 10 mg/kg QUE nanoparticle complex as a single abdominal subcutaneous injection every 5 days, continuously administered for 8 weeks to diabetic rats. Blood and left kidneys were collected; pathological change of kidney, renal function, oxidative stress level, blood glucose level, serum lipid, urine protein, and albumin/creatinine ratio were measured; and neutrophil adhesion, ICAM-1 expression, and CD11b+ cells infiltration were observed. Both QUE and QUE nanoparticle complex preconditioning ameliorated the pathological damage of kidney and improved renal function, alleviated renal oxidative stress injury, restricted inflammatory cells infiltration, and downregulated the ICAM-1 expression as compared to DN group, while QUE nanoparticle complex significantly alleviated this effect.
研究领域:
药理学
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分子生物学
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肾脏病学
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
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2019
·
IF 8.063
Xu-Qi Kang,Gao-Feng Shu,Sai-Ping Jiang,Xiao-Lin Xu,Jing Qi,Fei-Yang Jin,Di Liu,Yong-Hong Xiao,Xiao-Yang Lu,Yong-Zhong Du
The prevalence of antibiotic resistance and lack of alternative drugs have posed an increasing threat to public health. Here, we prepared β-Ga 2 O 3 :Cr 3+ nanoparticles modified with ICAM1-antibody-conjugated TPGS (I-TPGS/Ga 2 O 3 ) as a novel antibiotic carrier for the treatment of drug-resistant infections. Methods : I-TPGS/Ga 2 O 3 were firstly characterized by measuring particle size, morphology, crystal structure, drug loading capacity, and in vitro drug release behaviors. The in vitro antibacterial activities of I-TPGS/Ga 2 O 3 /TIG were evaluated using standard and drug-resistant bacteria. The internalization of I-TPGS/Ga 2 O 3 was observed by fluorescence confocal imaging, and the expression levels of the efflux pump genes of TRKP were analyzed by real-time RT-PCR. In vitro cellular uptake and in vivo biodistribution study were performed to investigate the targeting specificity of I-TPGS/Ga 2 O 3 using HUEVC and acute pneumonia mice, respectively. The in vivo anti-infective efficacy and biosafety of I-TPGS/Ga 2 O 3 /TIG were finally evaluated using acute pneumonia mice. Results : It was found that TPGS could down-regulate the over-expression of the efflux pump genes, thus decreasing the efflux pump activity of bacteria. I-TPGS/Ga 2 O 3 with small particle size and uniform distribution facilitated their internalization in bacteria, and the TPGS modification resulted in a significant reduction in the efflux of loaded antibiotics. These properties rendered the encapsulated tigecycline to exert a stronger antibacterial activity both in vitro and in vivo . Additionally, targeted delivery of I-TPGS/Ga 2 O 3 mediated by ICAM1 antibodies contributed to a safe and effective therapy. Conclusion : It is of great value to apply I-TPGS/Ga 2 O 3 as a novel and effective antibiotic delivery system for the treatment of drug-resistant infections.
研究领域:
药学
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生物医学工程
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微生物学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Advances
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2022
·
IF 0
Qiying Shen,Quan Hu,Ting Tang,Xiaoying Ying,Gaofeng Shu,Jiawei Shen,Chong Teng,Yongzhong Du
Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease without effective treatment. Tofacitinib (TOF) is a JAK inhibitor that can be used for RA therapy, but it still faces the problems of nonspecific distribution and relatively low therapeutic effect. Herein, ICAM-1-modified TOF-loaded P(AN-co-AAm)-PEG micelles (AI-TM) were developed, which can result in an enhanced RA therapy when combining with microwave hyperthermia (MH). It was found that AI-TM could rapidly release the encapsulated TOF under a thermal condition of >43 °C, which was due to the fact that the polymeric micelles has an upper critical solution temperature (UCST) of 43 °C. AI-TM could specifically distribute into the inflamed joints of RA mice, which is associated with the high affinity between anti-ICAM-1 and overexpressed ICAM-1 receptors. Moreover, the combination of AI-TM and MH could result in a remarkably enhanced anti-rheumatic activity, which was related to the RA-targeted ability of AI-TM, the rapid TOF release under MH, and the combined effect between TOF and MH treatment. Our study definitely provides a novel strategy for effective treatment of RA.
研究领域:
药理学
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生物医学工程
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
Nanoscale
·
2023
·
IF 6.7
Yu Ran,Shanmei Yin,Pei Xie,Yaxue Liu,ying wang,Zongning Yin
Acute Lung Injury (ALI) is an inflammatory disease caused by multiple factors such as infection, trauma, and chemicals. Without effective intervention during the early stages, it usually quickly progresses to acute respiratory distress syndrome (ARDS). Since ordinary pharmaceutical preparations cannot precisely target to the lungs, their clinical application is limited. In response, we constructed a γ3 peptide-decorated and ROS-responsive nanoparticle system encapsulating therapeutic dexamethasone (Dex/PSB-γ3 NPs). In vitro, Dex/PSB-γ3 NPs had rapid H2O2 responsiveness, low cytotoxicity, and strong intracellular ROS removal capacity. In a mouse model of ALI, Dex/PSB-γ3 NPs accumulated at the injured lung rapidly, alleviating pulmonary edema and cytokine levels significantly. The modification of NPs by γ3 peptide achieved highly specific positioning of NPs in the inflammatory area. The ROS-responsive release mechanism ensured the rapid release of therapeutic dexamethasone at the inflammatory site. This combined approach improves treatment accuracy, and drug bioavailability, and effectively inhibits inflammation progression. Our study could effectively reduce the risk of ALI progressing to ARDS and hold potential for the early treatment of ALI.
研究领域:
药理学
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纳米技术
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炎症
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呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Zhao Wenwen,Feng Haitao,Guo Shuhui,Han Yantao,Chen Xiuping
ICAM-1 overexpression and subsequent adhesion of leukocytes to endothelial cells play critical roles in the early stage of atherosclerosis. Danshenol A (DA) is an abietane-type diterpenoid isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. The mechanisms under its regulation of adhesion of molecular expression are explored. Here, the effect of DA on TNF-α-induced ICAM-1 expression was investigated in endothelial cells. TNF-α-induced ICAM-1 expression and subsequent adhesion of monocytes, as well as elevated reactive oxygen species (ROS) generation and NOX4 expression were all significantly reversed by DA, siNOX4 and NOX4 inhibitor GKT137831. Furthermore, TNF-α-induced ICAM-1 expression, which was increased via IKKβ/IκBα-mediated activation of NF-κB p65, was also inhibited by DA. Interestingly, NOX4 overexpression suppressed the ICAM-1 expression, and this finding may be ascribed to the activation of Nrf-2. Additionally, NF-κB inhibitor PDTC, siNOX4, or DA can decrease the TNF-α-induced ICAM-1 expression and suppress the adhesion of monocytes. In all, DA inhibited TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion to endothelial cells through the NOX4-dependent IKKβ/NF-κB pathway. Besides, NOX4 played dual role in regulating ICAM-1 expression via diverse signal pathway. This novel bioactivity will make DA a good candidate to be further explored for therapeutic or preventive application for atherosclerosis.
研究领域:
药理学
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心血管疾病
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2018
·Vol. 16
·期 1
·1-14
·
IF 5.294
Li Shujuan,Chen Li,Wang Guokang,Xu Lexing,Hou Shanshan,Chen Ziwei,Xu Xiaoling,Wang Xiaojuan,Liu Fuhe,Du Yong-Zhong
Background Acute lung injury (ALI) is a life-threatening clinical syndrome without effective treatment. Targeting delivery of glucocorticoid to lung shows potential efficacy for ALI based on their anti-inflammatory and anti-fibrotic properties, breaking through their clinical application limitation due to systemic side effects. This work was aimed to establish lung-targeted dexamethasone (DEX) loaded nanostructured lipid carriers (NLCs) with opposite surface charge and investigate their therapeutic effects on lipopolysaccharide (LPS)-induced ALI mice.Results The diameter of anionic anti-intercellular adhesion molecule 1 (anti-ICAM-1) antibody-conjugated DEX-loaded NLCs (ICAM/DEX/NLCs) and the cationic ones with octadecylamine (ODA) modification (ICAM/DEX/ODA-NLCs) was about 249.9 and 235.9 nm. The zeta potential of ICAM/DEX/NLCs and ICAM/DEX/ODA-NLCs was about − 30.3 and 37.4 mV, respectively. Relative to the non-targeted control and ICAM/DEX/ODA-NLCs, ICAM/DEX/NLCs exhibited higher in vitro cellular uptake in LPS-activated human vascular endothelial cell line EAhy926 after CAM-mediated endocytosis, and stronger in vivo pulmonary distribution in the ALI model mice. In vivo i.v. administration of ICAM/DEX/NLCs significantly attenuated pulmonary inflammatory cells infiltration, and the production of pro-inflammatory cytokine TNF-α and IL-6 in ALI mice. H&E stain also revealed positive histological improvements by ICAM/DEX/NLCs.Conclusion sICAM/DEX/NLCs may represent a potential pulmonary endothelium targeted device, which facilitate translation of DEX into clinical ALI treatment.
研究领域:
药学
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肺科学
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纳米技术
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免疫学
·
治疗学
✓ 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
·
免疫学
·
心血管研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2023
·
IF 12.6
Zhijun Lin,Mengyao Liu,Wei Xing,Feng-Hua Wang,Hongxia Zhang,Xiao-Li Wei,Hans Schmitthenner,Xi Xie,Xiaojun Xia,Jiang Yang
Sensitive and accurate biomarker-driven assay guidance has been widely adopted to identify responsive patients for immune checkpoint blockade (ICB) therapy to impede disease progression and extend survival. However, most current assays are invasive, requiring surgical pathology specimens and only informing monochronic information. Here, we report a multiplexed enhanced fluorescence microarray immunoassay (eFMIA) based on a nanostructured gold nanoisland substrate (AuNIS), which macroscopically amplifies near-infrared fluorescence (NIRF) of a structurally symmetric IRDye78 fluorophore by over two orders of magnitude of 202.6-fold. Aided by non-contact piezo-driven micro-dispensing (PDMD), eFMIA simultaneously and semi-quantitatively detected intracellular and secreted programmed death-ligand 1 (PD-L1) and intercellular adhesion molecule-1 (ICAM-1) in human nasopharyngeal carcinoma (NPC) cells. The assay performance was superior to fluorescence immunoassays (FIA) and enzyme-linked immunosorbent assays (ELISA), with lower detection limits. Using eFMIA, we found significantly differential levels of soluble PD-L1 (sPD-L1) and sICAM-1 in the sera of 28 cancer patients, with different clinical outcomes following anti-PD-1 ICB therapy. With a well-characterized mechanism, the high-performance plasmonic multiplexed assay with the composite biomarkers may be a valuable tool to assist clinicians with decision-making and patient stratification to afford predictive ICB therapy responses.
研究领域:
癌症生物学
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免疫学
·
生物医学工程
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INFLAMMOPHARMACOLOGY
·
2024
·
IF 4.6
Iqbal Urooj,Malik Abdul,Sial Nabeela Tabassum,Mehmood Malik Hassan,Nawaz Shoaib,Papadakis Marios,Fouad Dalia,Ateyya Hayam,Welson Nermeen N.,Alexiou Athanasios,Batiha Gaber El-Saber
Background The current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of β- Citronellol using in vitro , in vivo assays and in silico approaches. Methods In vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1 ml from 1% w/v) and Formaldehyde (0.1 ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of β-Citronellol at 25, 50, and 100 mg/kg, using indomethacin-induced (25 mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE 2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA). Results β - Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400 µg/mL. Citronellol decreased rat’s paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE 2 , and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β - Citronellol (50 and 100 mg/kg) increased gastric PGE 2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues. Conclusions The anti-inflammatory, anti-oxidant, and gastro-protective effects of β - Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE 2, 5-LOX, eNOS, and ICAM-1 inflammatory markers. Graphical abstract
研究领域:
药理学
·
炎症
·
胃肠病学
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分子生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cellular and Molecular Bioengineering
·
2019
·Vol. 13
·期 1
·99-112
·
IF 2.477
Wang Yue,Li Xiaoli,Liu Lanlan,Liu Bingruo,Wang Feng,Chen Changsheng
Introduction Ultrasound-targeted microbubble destruction (UTMD) has been shown a promising approach for target-specific gene delivery and treatment of many diseases in the past decade. To improve the therapeutic potential of UTMD, the gene carrier of microbubbles should possess adequate DNA condensation capability and (or) specific cell or tissue selectivity. The tissue-targeted and ultrasound-targeted cationic microbubbles were developed to meet gene therapy. Methods A tissue-targeted stearic acid-inserted cationic microbubbles (SCMBs) were prepared for ultrasound-targeted gene delivery. Branched PEI was modified with stearic acid and further mixed with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and biot-1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N -[methoxy (polyethylene glycol)-2000] (ammonium salt) (Biot-DSPE-PEG2000), intercellular adhesion molecule-1 (ICAM-1) antibody and plasmid DNA to prepare cationic microbubbles through ultrasonic hydration. The ICAM-1 antibody and plasmid DNA were expected to assemble to the surface of SCMBs via biotin-avidin interaction and electrostatic interaction, respectively. Results It was found that the SCMBs had higher zeta potential compared with neutral microbubbles (NMBs) and cationic microbubbles (CMBs). In contrast, DNA incorporated SCMBs4 showed negative potential, exhibiting good DNA-binding capacity. Confocal images showed that the HeLa cells were attached around by the SCMBs4 from the view of green fluorescence of fluorescein isothiocyanate-loaded IgG which conjugated to ICAM-1 antibody on their surface. After ultrasound treatment, HeLa cells treated with SCMBs exhibited slightly stronger red fluorescence under confocal laser scanning microscope, indicating a synergistic promotion for transfection efficiency. Conclusions This tissue- and ultrasound-targeted cationic microbubble demonstrated here showed a promising strategy for improving gene therapy in the future.
研究领域:
生物医学工程
·
基因治疗
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药学
✓ 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
·
代谢组学
·
生物化学
·
药物化学
·
植物科学
✓ 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）