Nanoscale
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2021
·Vol. 13
·期 47
·20170-20185
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IF 7.79
Yanqin Song,Muhammad Ismail,Qi Shan,Jianing Zhao,Yanping Zhu,Leiming Zhang,Yuan Du,Longbing Ling
Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder that has seriously affected human health worldwide and its current management requires more successful therapeutic approaches. The combination of nanomedicines and pathophysiology into one system may provide an alternative strategy for precise RA treatment. In this work, a practical ROS-mediated liposome, abbreviated as Dex@FA-ROS-Lips that comprised synthetic dimeric thioether lipids (di-S-PC) and a surface functionalized with folic acid (FA), was proposed for dexamethasone (Dex) delivery. Incorporation with thioether lipids and a FA segment significantly improved the triggered release and improved the triggered release of cytotoxic Dex as well as the active targeting of RA, altering its overall pharmacokinetics and safety profiles in vivo. As proof, the designed Dex@FA-ROS-Lips demonstrated effective internalization by LPS-activated Raw264.7 macrophages with FA receptor overexpression and released Dex at the inflammatory site due to the ROS-triggered disassembly. Intravenous injection of this Dex@FA-ROS-Lips into adjuvant-induced arthritis (AIA) mice led to its incremental accumulation in inflamed joint tissues and significantly alleviated the cartilage destruction and joint swelling via suppression of proinflammatory cytokines (iRhom2, TNF-α and BAFF), as compared to the effect of commercial free Dex. Importantly, the Dex@FA-ROS-Lips nanoformulation showed better hemocompatibility with less adverse effects on the body weight and immune organ index of AIA mice. The anti-inflammatory mechanism of Dex@FA-ROS-Lips was further studied and it was found that it is possibly associated with the down-regulation of iRhom2 and the activation of the TNF-α/BAFF signaling pathway. Therefore, the integration of nanomedicines and the RA microenvironment using multifunctional Dex@FA-ROS-Lips shall be a novel RA treatment modality with full clinical potential, and based on the enhanced therapeutic effect, the signaling pathway of iRhom2/TNF-α/BAFF reasonably explained the mechanism of Dex@FA-ROS-Lips in anti-RA, which suggested a molecular target for RA therapy and other inflammatory diseases.
研究领域:
药理学
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纳米技术
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免疫学
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风湿病学
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AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
·
2024
·Vol. 327
·期 1
·C1
·
IF 5
Yangyang Wang,Zhiming Xiu,Kuo Qu,Liying Wang,Huiyan Wang,Yongli Yu
Download figureDownload PowerPoint The purpose of this study is to investigate the previously unknown connection that succinate has with neutrophils in the setting of adjuvant-mediated immunological enhancement. It has been discovered that succinates stimulate the recruitment of neutrophils in immunization sites, which in turn induces the expression of what is known as neutrophil-derived B cell-activating factor (BAFF). Further amplification of vaccine-induced antibody responses is provided via the succinate receptor 1-interferon regulatory factor 5 (SUCNR1-IRF5)-BAFF signaling pathway, which provides insights into a unique mechanism for immunological enhancement. NEW & NOTEWORTHY This study explores the role of succinate as a vaccine adjuvant, revealing its capacity to enhance neutrophil recruitment at immunization sites, which boosts B cell activation through the succinate receptor 1-interferon regulatory factor 5-B cell-activating factor (SUCNR1-IRF5-BAFF) signaling pathway. Results demonstrate succinate’s potential to amplify vaccine-induced antibody responses, highlighting its significance in immunological enhancement and offering new insights into the adjuvant mechanisms of action, particularly in neutrophil-mediated immune responses.
研究领域:
免疫学
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疫苗学
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分子生物学
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JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2024
·
IF 2
Wanyu Gao,Yuan Gao,Ziping Yin,Yanfei Sun,Yu Zhang,Longyi Zhu,Jun Luo
The solubility of 3,4-bis(4′-aminofurazan-3′-yl)furoxan (BAFF) was determined in ten pure solvents (dichloromethane, 1,2-dichloroethane, cyclohexane, water, methanol, ethanol, n-propanol, isopropanol, n-butanol, and ethyl acetate) as well as three binary solvent mixtures (methanol/water, ethanol/water, ethyl acetate/1,2-dichloroethane) over various temperature ranges (283.15 to 353.15 K). The measurements were conducted by using a static analytical method under atmospheric pressure. During the temperature ranges investigated, it was observed that the solubility of BAFF increased with the increase in the temperature in all selected solvents. Among the ten pure solvents, ethyl acetate has the highest solubility, while methanol, ethanol, n-butanol, and isopropanol have moderate solubilities. Water, 1,2-dichloroethane, and dichloromethane have relatively low solubilities, while in the binary solvent systems, the solubility of BAFF decreased with increasing the mole fraction of antisolvent (water or 1,2-dichloroethane) at given temperature. Moreover, the experimental solubility data in pure solvents were correlated using the modified Apelblat equation, the λh equation, and two local composition models (Wilson model and NRTL model). Additionally, the modified Apelblat equation, CNIBS/R-K model, Jouyban-Acree model, and multicomponent NRTL model were successfully employed to correlate the experimental solubility in mixed solvent systems. Furthermore, based on the experimental data and the NRTL model, the dissolution thermodynamic properties of BAFF in both pure and binary solvents were calculated and analyzed. These properties include the dissolution Gibbs energy, enthalpy, and entropy. These data indicate that the dissolution process of BAFF is endothermic and spontaneous.
研究领域:
化学
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物理化学
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材料科学
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ACS Omega
·
2026
·
IF 5.2
Jin Hu,Yeshuang Yuan,Jing Li,Shanbo Yang,Jiaqi Sun,Wei Song,Lulu Liu,Hua Bai,Bo Zhang
B-cell-activating factor (BAFF) plays a fundamental role in B lymphocyte survival and homeostasis, and aberrant BAFF signaling is closely related to numerous autoimmune disorders. Although passive immunization strategies using monoclonal antibodies and engineered receptors have achieved success in treating autoimmune diseases, disadvantages, including the cost of continuous administration and potential immunogenicity, still exist. Here, we report an innovative active anti-BAFF vaccine that was developed through the site-specific incorporation of the unnatural amino acid p-nitrophenylalanine (pNO2-Phe) in soluble murine BAFF (DmBAFF). It triggered a humoral immune response against endogenous BAFF and successfully alleviated collagen-induced arthritis in a murine model. An analysis of the immune response to the pNO2-Phe-containing DmBAFF mutants in both DBA/1(H2q) and C57BL/6 (H2b) mice indicated that the mutants disrupted both T cell and B-cell tolerance toward the endogenous molecule and resulted in the production of strong and distinct antibodies against the corresponding modified epitopes of WT-mBAFF. Preventive vaccination with DmBAFF containing pNO2-Phe at Y91 or Y139 significantly reduced the arthritis incidence and joint inflammation compared with DmBAFF but did not obviously affect T and B-cell subpopulations. Based on these data collectively, preventive vaccination with BAFF containing the site-specific incorporation of pNO2-Phe is an effective prophylactic intervention option for autoimmune arthritis. The therapeutic potential of this vaccine after disease onset remains to be evaluated.
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