International Journal of Nanomedicine
·
2026
·
IF 8.7
Zhiyuan Luo,Luyu Jia,Yu Tang,Yifan Huang,Zhanni Ma,Youpeng Li,Xiaojing Zhang,Pengfei Zhang,Tian Xie
Purpose Inflammatory bowel disease (IBD) is a chronic condition driven by pro-inflammatory macrophages. Although natural compounds with carbon–carbon double bonds (C=C bonds), such as β‑elemene, exhibit anti-inflammatory properties, their precise subcellular targets and mechanisms remain elusive. This study aimed to develop a targeted nanomedicine to elucidate the anti-inflammatory mechanism of β‑elemene and establish a novel therapeutic strategy for colitis.Patients and Methods We engineered a reactive oxygen species (ROS)-responsive β‑elemene nanoemulsion (ELE-NE) for targeted drug delivery. Its therapeutic efficacy and mechanism were evaluated in a murine model of dextran sulfate sodium (DSS)-induced colitis. A mitochondria-targeted, ROS-activatable near-infrared probe was also developed for in vivo imaging tracking of inflammatory foci and assessment of therapeutic efficacy.Results In DSS-induced colitis mice, ELE-NE preferentially accumulated in inflamed colon tissue and effectively alleviated disease pathology. Mechanistically, upon reaching inflammatory macrophages, ELE-NE utilized the pathological ROS surge to undergo spatially confined aggregation at mitochondrial sites. This nano-aggregation directly disrupted the electron transport chain (ETC), potently suppressing oxidative phosphorylation and reprogramming cellular energy metabolism. Consequently, this mitochondria-focused metabolic intervention attenuated M1 macrophage polarization, reduced pro-inflammatory cytokine secretion.Conclusion This is the first report demonstrating that β‑elemene acts via ROS‑triggered mitochondrial aggregation and metabolic reprogramming. We deciphered the mechanism of β-elemene, revealing that its olefinic (C=C) functional group enables bioresponsive mitochondrial aggregation and metabolic reprogramming, thereby proposing the concept of “olefinic drugs” as a distinct therapeutic class. Furthermore, we established a novel theranostic paradigm for treating inflammatory diseases using olefinic nanomedicines, enabled by a companion imaging tool for non‑invasive detection of inflammatory foci and dynamic monitoring of the treatment process.
✓ 已验证
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2019
·Vol. 9
·期 3
·667-678
·
IF 3.111
Zhang Qian,Tian Xin,Cao Xiufeng
In this study, we developed an intravenously injectable, transferrin-functionalised microemulsion that simultaneously carries β-elemene and celastrol (called Tf-EC-MEs) for enhanced anti-lung cancer treatment and reduced systemic toxicity. These dual-drug-loaded Tf-EC-MEs not only displayed synergistic antiproliferative effects on cultured cells in vitro, but also showed enhanced efficacy in vivo via active tumour targeting. In preparatory experiments, we found that β-elemene was capable of being used as oil phase, which enhanced drug-loading efficiency and allowed the mass ratio of β-elemene and celastrol to be optimised. In cellular studies, Tf-EC-MEs exhibited significantly improved A549 cellular uptake compared with β-elemene+celastrol (conventional combination treatment) and EC-MEs (non-active targeted treatment), demonstrating remarkable synergistic antiproliferative effects and higher rates of cell apoptosis. In A549-bearing xenograft mouse tumour models, Tf-EC-MEs exhibited enhanced antitumour activity compared to all other treatments. More importantly, Tf-EC-MEs did not cause the obvious systemic toxicity commonly found with mono-celastrol treatment. Collectively, these findings suggest that Tf-EC-MEs are a promising strategy for the combination drug treatment of lung cancer.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Cancer Research
·
2022
·
IF 5.942
Guangyu Cheng,Lin Li,Qingjie Li,Shulin Lian,Hongbo Chu,Yunlu Ding,Chikun Li,Yan Leng
Multi-drug resistance remains a critical issue in cancer treatment that hinders the effective use of chemotherapeutic drugs. The active components of traditional Chinese medicine have been applied as adjuvants to accentuate the anticancer properties of conventional drugs such as cisplatin. However, their application requires further validation and optimization. This study explored the anticancer activity of β-elemene, a natural component of traditional Chinese medical formulations. The effect of β-elemene on the anticancer properties of cisplatin was evaluated in A549 and NCI-H1650 lung cancer cells. Cell apoptosis, stem-like properties, glucose metabolism, multi-drug resistance, and PI3K/AKT/mTOR activation were assessed via flow cytometry, tumorsphere formation, and western blotting. The target genes of β-elemene were predicted using bioinformatics tools and validated in both cell lines. A xenograft model of lung cancer was established in nude mice to evaluate the combined effects of β-elemene and cisplatin in vivo . We found that β-elemene acted synergistically with cisplatin against non-small cell lung cancer cells by promoting apoptosis and impairing glucose metabolism, multi-drug resistance, and stemness maintenance. These effects were mediated by the inhibition of PI3K/AKT/mTOR activation. Bioinformatics analysis revealed that RB1 and TP53 are common target genes associated with lung cancer and β-elemene. The anti-tumorigenic properties of β-elemene were confirmed in vivo , wherein β-elemene, along with cisplatin, significantly suppressed tumor growth in a mouse xenograft model of non-small cell lung cancer. As such, β-elemene acted as an inhibitor of PI3K/AKT/mTOR signaling and enhanced the anticancer effect of cisplatin by targeting tumor metabolism, chemoresistance, and stem-like behavior. Thus, β-elemene is an effective anticancer adjuvant agent with potential clinical applications.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
生物信息学
✓ 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）