{"title":"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。","authors":"Khaled Mahmoud, Mahmoud Teaima, Yasmeen Attia, Mohamed El-Nabarawi, Shady Swidan","doi":"10.1080/17425247.2023.2216451","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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 <i>in vitro</i> and <i>in vivo</i>. The anti-migratory potential and EMT suppression through PTEN/AKT axis modulation were also explored.</p><p><strong>Results: </strong>SIM-LNC50 was superior to SIM-LNC25 in both <i>in vitro</i> and <i>in vivo</i> 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 <i>in vitro</i> and <i>in vivo</i>. PTEN/AKT axis modulation was also evident with SIM-LNC50.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":"20 5","pages":"703-719"},"PeriodicalIF":5.0000,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Size-optimized simvastatin-loaded TPGS modified lipid nanocapsules for targeting epithelial-to-mesenchymal transition in hepatocellular carcinoma: Role of PTEN/AKT signaling.\",\"authors\":\"Khaled Mahmoud, Mahmoud Teaima, Yasmeen Attia, Mohamed El-Nabarawi, Shady Swidan\",\"doi\":\"10.1080/17425247.2023.2216451\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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 <i>in vitro</i> and <i>in vivo</i>. The anti-migratory potential and EMT suppression through PTEN/AKT axis modulation were also explored.</p><p><strong>Results: </strong>SIM-LNC50 was superior to SIM-LNC25 in both <i>in vitro</i> and <i>in vivo</i> 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 <i>in vitro</i> and <i>in vivo</i>. PTEN/AKT axis modulation was also evident with SIM-LNC50.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":12229,\"journal\":{\"name\":\"Expert Opinion on Drug Delivery\",\"volume\":\"20 5\",\"pages\":\"703-719\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2023-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Drug Delivery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17425247.2023.2216451\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/5/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17425247.2023.2216451","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/5/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.