尺寸优化的辛伐他汀负载TPGS修饰脂质纳米胶囊用于靶向肝细胞癌的上皮-间质转化:PTEN/AKT信号转导的作用。

IF 5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Drug Delivery Pub Date : 2023-05-01 Epub Date: 2023-05-30 DOI:10.1080/17425247.2023.2216451
Khaled Mahmoud, Mahmoud Teaima, Yasmeen Attia, Mohamed El-Nabarawi, Shady Swidan
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引用次数: 0

摘要

研究目的制备了新型D-α-生育酚聚乙二醇1000琥珀酸酯(TPGS)修饰的脂质纳米胶囊(LNC),旨在提高辛伐他汀(SIM)对肝细胞癌(HCC)的疗效。因此,本研究试图探讨尺寸优化的SIM负载LNC对HCC上皮细胞向间质转化(EMT)的影响,从而深入了解磷酸酶和天丝蛋白同源物(PTEN)/蛋白激酶B(AKT)轴的影响:方法:制备了粒径为25 nm(SIM-LNC25)和50 nm(SIM-LNC50)的两种优化SIM负载LNC,并进行了生物分布研究。对所制备的 LNC 的抗癌效果进行了体外和体内评估。结果显示,SIM-LNC50优于SIM-LNC25:结果:SIM-LNC50在体外和体内实验中均优于SIM-LNC25,细胞毒性测定、肿瘤组织病理学和凋亡增强都证明了这一点。SIM-LNC50 还能减轻 HCC 细胞的迁移潜力。此外,EMT标记物意味着肿瘤细胞在体外和体内都向上皮表型而非间充质表型转变。SIM-LNC50对PTEN/AKT轴的调节作用也很明显:因此,本研究表明,SIM-LNC50 纳米颗粒通过调节 PTEN/AKT 信号轴靶向 EMT,对 HCC 具有疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Size-optimized simvastatin-loaded TPGS modified lipid nanocapsules for targeting epithelial-to-mesenchymal transition in hepatocellular carcinoma: Role of PTEN/AKT signaling.

Objectives: Novel D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified lipid nanocapsules (LNC) were prepared with the aim of improving the effectiveness of simvastatin (SIM) in hepatocellular carcinoma (HCC). The present study, therefore, sought to investigate the effect of size-optimized SIM-loaded LNC on epithelial-to-mesenchymal transition (EMT) in HCC, providing insights on the implication of phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) axis.

Methods: Two optimized SIM-loaded LNCs with particle sizes 25 nm (SIM-LNC25) and 50 nm (SIM-LNC50) were prepared and biodistribution studies were performed. The anticancer effect of the prepared LNC was evaluated both in vitro and in vivo. The anti-migratory potential and EMT suppression through PTEN/AKT axis modulation were also explored.

Results: SIM-LNC50 was superior to SIM-LNC25 in both in vitro and in vivo experiments, as evidenced by cytotoxicity assays, tumor histopathology, and enhanced apoptosis. SIM-LNC50 also alleviated the migratory potential of HCC cells. Moreover, EMT markers implied a transition of tumor cells toward the epithelial rather than the mesenchymal phenotype both in vitro and in vivo. PTEN/AKT axis modulation was also evident with SIM-LNC50.

Conclusion: The present study, therefore, suggests the efficacy of the 50 nm particles in SIM-loaded LNC in HCC by targeting EMT via modulating the PTEN/AKT signaling axis.

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来源期刊
CiteScore
11.10
自引率
3.00%
发文量
104
审稿时长
3 months
期刊介绍: Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
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