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Biomaterials Science · 2018 ·Vol. 6 ·期 12 ·3284-3299 · IF 5.831

Non-triggered sequential-release liposomes enhance anti-breast cancer efficacy of STS and celastrol-based microemulsion

Ding Qu,Lixiang Wang,Yue Qin,Mengfei Guo,Jian Guo,Mengmeng Huang,Yuping Liu,Congyan Liu,Hui Li,Yan Chen

A codelivery system that sequentially releases its contents is an effective strategy to enhance anticancer efficacy. Here, we fabricated multicomponent-based liposomes (T/CM-L) loaded with sodium tanshinone IIA sulfonate (STS) and a small-sized microemulsion of celastrol (CM), which shows synergistic anti-breast cancer activity through the initial release of STS for modulation of the tumor microenvironment, and subsequent release of CM (and its payloads) for eradication of tumor tissues. In vitro studies exhibited that T/CM-L induced massive apoptosis of MCF-7 cells, indicating a coordinated cytotoxicity against cancer cells. Once the liposomes had accumulated at the tumor site, STS was released from T/CM-L in the first place to repair abnormal vessels as well as to decrease the level of fibroblasts. Owing to the barriers of the microemulsion and the liposomes, the celastrol was then unloaded at a moderate rate to kill the tumor cells, which resulted in the shrinkage of the tumor size. Furthermore, T/CM-L displayed diminished systemic toxicity compared to celastrol used alone. Our work offers a novel strategy for combination anticancer treatment and holds promising potential not only for breast cancer treatment, but also for the treatment of other solid tumors.

研究领域: 药学 · 肿瘤学 · 药物递送系统 · 生物医学工程
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JOURNAL OF ETHNOPHARMACOLOGY · 2022 · IF 5.195

Integrated metabolomics and network pharmacology to reveal the therapeutic mechanism of Dingkun Pill on polycystic ovary syndrome

Ying-Li Cai,Feng Zhang,Xiu-Xiu Dou,Hua-Wu Zeng,Gao-Song Wu,Yan-Lin Liang,Xi-Ke Xu,Jing Zhao,Ji Ye,Wei-Dong Zhang

Ethnopharmacological relevance Dingkun Pill (DKP), a traditional Chinese medicine prescription, was modified from Bujing decoction and Xusijiangsheng pill by the imperial physician in the Qing dynasty (1700′ s). It was believed to treat various gynecological diseases by nourishing qi and blood. Accumulating evidence indicates that it is effective in treating polycystic ovary syndrome (PCOS). However, the therapeutic efficacy and mechanism of action DKP against PCOS need to be further elucidated. Aim of the study To investigate the therapeutic effect and action mechanism of DKP against PCOS using an integrated approach of metabolomics and network pharmacology . Materials and methods The rat model of PCOS was established by dehydroepiandrosterone . An integrated metabolomics and network pharmacology strategy was applied to systemically clarify the mechanism of DKP against PCOS. Theca cells were prepared to evaluate the effect of DKP and its ingredients on testosterone synthesis in vitro. Results The pharmacological experiments demonstrated that DKP could effectively convert the disordered estrous cyclicity, decrease the level of testosterone and the luteinizing hormone/follicle stimulating hormone ratio, and inhibit abnormal follicle formation in PCOS rats. By metabolomics analysis, 164 serum endogenous differential metabolites and 172 urine endogenous differential metabolites were tentatively identified. Steroid hormone biosynthesis and ovarian steroidogenesis were the most significantly impacted pathways. Based on network pharmacology and metabolomics studies, the ingredient-target-pathway network of DKP in the treatment of PCOS was constructed. Among the 10 key targets, CYP17A1 , CYP19A1 , STS, AR, ESR1, and MYC were closely involved in ovarian androgen synthesis. In theca cell-based assay of testosterone synthesis, DKP and its two active compounds (ligustilide and picrocrocin) showed inhibitory effects. Conclusion DKP effectively improved symptoms in rats with dehydroepiandrosterone-induced PCOS. The mechanism of DKP in the treatment of PCOS is related to the CYP17A1 enzyme required for androgen synthesis.

CAS / MDL: 53-43-0
研究领域: 药理学 · 中医 · 妇科 · 代谢组学 · 网络药理学
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COMPOSITES COMMUNICATIONS · 2025 · IF 7.7

Low-dose STS–PEG–chitosan coating on PLCL scaffolds: A multifunctional strategy for endothelialization, anti-inflammation, and antithrombosis in vascular grafts

Yutong Liu,Xiaolin Sun,Yunhuan Li,Kuihua Zhang,Zhiyong Yan,Changlin Zhai,Jinglei Wu,Anlin Yin

The long-term success of small-diameter vascular grafts remains limited by thrombosis, chronic inflammation, and poor endothelialization. To address these challenges, we developed a multifunctional coating strategy by integrating polyethylene glycol–chitosan (PEG–CS) with low-dose sodium tanshinone IIA sulfonate (STS, 0.01 %) on poly(L-lactide-co-ε-caprolactone) (PLCL) scaffolds. The PEG–CS/STS coating significantly improved hydrophilicity and structural stability, while providing bioactivity that promoted endothelial cell proliferation and alignment. In vitro studies demonstrated markedly reduced platelet adhesion and activation, along with a favorable shift in macrophage polarization toward the anti-inflammatory M2 phenotype. These synergistic effects create a vascular-friendly microenvironment that promotes endothelialization and suppresses thrombosis and inflammation. PEG reduces platelet adsorption, allowing STS to exert its anti-inflammatory effects, while chitosan’s electrostatic interaction with STS supports its stable loading and controlled release, enhancing its bioactivity. Our findings highlight that the PEG-CS/STS modified scaffold effectively integrates endothelialization, immunomodulation, and antithrombotic protection, representing a promising next generation strategy for small diameter vascular grafts.

CAS / MDL: 25322-68-3 920-66-1
研究领域: 生物医学工程 · 组织工程 · 血管生物学 · 生物材料 · 再生医学
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