International Journal of Nanomedicine
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2024
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IF 6.6
Pilong Shi,Yuetong Sha,Xinran Wang,Tao Yang,Jiawei Wu,Jiajun Zhou,Kai Liu,Xue Guan,Song Wang,Yongsheng Liu,Jingquan Gao,Hongli Sun,Tao Ban,Yonggang Cao
Purpose Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.Methods In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.Results Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.Conclusion Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2.
研究领域:
心血管疾病
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纳米技术
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 10
·1263
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IF 5.5
Jin Xue,Zifan Qiao,Shiyu Huang,Mubarak G. Bello,Lihua Chen
Background/Objectives:Ulcerative colitis (UC) involves chronic colon inflammation and oxidative stress. Treating UC is challenging due to systemic drug side effects and poor targeted delivery. Nanocarriers responsive to the UC microenvironment, particularly elevated reactive oxygen species (ROS), could overcome these limitations. This study developed an oral delivery system for ROS-triggered drug release and active targeting. Using ferulic acid (FER), a system was designed to enhance site-specific accumulation and therapeutic efficacy against colitis.Methods:A ROS-sensitive covalent organic framework (COF) was synthesized from γ-cyclodextrin and functionalized with folic acid (FA) to create a carrier (COF-FA) designed for potential active targeting. This carrier was loaded with FER to form FER@COF-FA. The system was characterized (SEM, FTIR, TGA), and its ROS scavenging and sustained drug release profiles were confirmed in vitro. Biocompatibility was evaluated in cell lines, and therapeutic efficacy was tested in a DSS-induced murine colitis model.Results:The synthesized FER@COF-FA demonstrated high drug loading, potent ROS-scavenging capability, and a sustained drug release profile. It showed excellent biocompatibility and, in the murine model, significantly outperformed free FER. Treatment alleviated disease severity, prevented colon shortening, restored healthy tissue histology, and rebalanced pro- and anti-inflammatory cytokines.Conclusions:The FER@COF-FA system represents a highly promising therapeutic strategy for UC. Its superior efficacy is attributed to a synergistic multi-mechanism approach, combining sustained release, ROS-responsive drug delivery, intrinsic antioxidant activity, and potential folate receptor-mediated targeting, which collectively enhance site-specific accumulation and therapeutic outcomes in the inflammatory colon microenvironment.
研究领域:
纳米医学
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炎症性肠病
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药物递送系统
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生物材料
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氧化应激
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胃肠药理学
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2023
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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
危险品化学品经营许可证（带存储）