[脂质体联合递送槲皮素和多柔比星通过调节上皮-间质转化过程抑制视网膜母细胞瘤]。

Q3 Pharmacology, Toxicology and Pharmaceutics Zhongguo Zhongyao Zazhi Pub Date : 2024-07-01 DOI:10.19540/j.cnki.cjcmm.20240319.301
Min Lin, Xiu-Mei Liu, Nian-Ping Feng, Ya-Qi Lyu
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引用次数: 0

摘要

调控上皮-间质转化(EMT)过程是抑制肿瘤生长和转移的重要策略。本研究基于视网膜母细胞瘤的EMT过程,构建了槲皮素(QUE)和多柔比星(DOX)共载脂质体(QD Lipo),探讨QUE和DOX联合治疗视网膜母细胞瘤的疗效和机制。为了优化 QD 脂质体的处方工艺,研究人员进行了单因素实验。最终得到直径为(108.87±1.93)nm、PDI为0.13±0.02、Zeta电位为(-34.83±1.92)mV的球形颗粒。QUE和DOX的包封率分别为96.20%±4.40%和91.17%±4.41%。以 Y79 人视网膜母细胞瘤细胞为体外细胞模型,共聚焦显微镜观察表明 QD 脂质体能提高 Y79 细胞的吸收效率。CCK-8测定证实,QUE和DOX的最佳联合治疗效果发生在质量比为1∶1到1∶2时。流式细胞术显示,QD Lipo 能增强 Y79 细胞的凋亡诱导作用。Western 印迹分析显示,QD Lipo 能显著降低 EMT 通路相关蛋白波形蛋白和 α-SMA 的表达。荧光检测发现,经 QD 处理后,Y79 细胞中的 ROS 水平明显下降。这些结果表明,QUE和DOX的脂质体联合给药能提高对视网膜母细胞瘤细胞的给药效率,通过下调ROS水平抑制视网膜母细胞瘤的EMT过程,并增强DOX对视网膜母细胞瘤的细胞毒性。
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[Liposome co-delivery of quercetin and doxorubicin in inhibiting retinoblastoma by regulating epithelial-mesenchymal transition process].

Regulating the process of epithelial-mesenchymal transition(EMT) is an essential strategy to inhibit tumor growth and metastasis. This study is based on the EMT process of retinoblastoma and constructs quercetin(QUE) and doxorubicin(DOX) co-loaded liposome(QD Lipo) to investigate the therapeutic effect and mechanisms of combined QUE and DOX treatment on retinoblastoma. Single-factor experiments were conducted to optimize the prescription process of QD Lipo. Eventually, spherical particles with a diameter of(108.87±1.93) nm, a PDI of 0.13±0.02, and a Zeta potential of(-34.83±1.92) mV were obtained. The encapsulation rates of QUE and DOX were 96.20%±4.40% and 91.17%±4.41%, respectively. Y79 human retinoblastoma cells were used as an in vitro cellular model, and confocal microscopy demonstrated that QD Lipo could enhance Y79 uptake efficiency. The CCK-8 assay confirmed that the optimal combination therapy effect of QUE and DOX occurred at a mass ratio of 1∶1 to 1∶2. Flow cytometry showed that QD Lipo enhanced the induction of apoptosis in Y79 cells. Western blot analysis revealed that QD Lipo significantly reduced the expression of EMT pathway-related proteins vimentin and α-SMA. Fluorescence assays detected a significant decrease in ROS levels in Y79 cells after treatment with QD. These results indicated that liposomal co-delivery of QUE and DOX can enhance drug delivery efficiency to retinoblastoma cells, inhibit the EMT process in retinoblastoma by downregulating ROS levels, and enhance the cytotoxicity of DOX against retinoblastoma.

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来源期刊
Zhongguo Zhongyao Zazhi
Zhongguo Zhongyao Zazhi Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
1.50
自引率
0.00%
发文量
581
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