Size-optimized simvastatin-loaded TPGS modified lipid nanocapsules for targeting epithelial-to-mesenchymal transition in hepatocellular carcinoma: Role of PTEN/AKT signaling

ABSTRACT

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.

KEYWORDS:

• Simvastatin
• TPGS
• lipid nanocapsules
• hepatocellular carcinoma
• EMT
• PTEN/AKT

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425247.2023.2216451

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conception and design: Mahmoud Teaima, Yasmeen Attia, Mohamed El-Nabarawi, Shady Swidan. Methodology: Khaled Mahmoud, Yasmeen Attia. Analysis, investigation, and interpretation of the data: Khaled Mahmoud, Mahmoud Teaima, Yasmeen Attia, Mohamed El-Nabarawi, Shady Swidan. Drafting of the manuscript: Khaled Mahmoud, Yasmeen Attia. Revising the manuscript critically for intellectual content: Mahmoud Teaima, Mohamed El-Nabarawi, Shady Swidan. The final approval of the version to be published: All authors: Mohamed El-Nabarawi, Mahmoud Teaima, Shady Swidan, Yasmeen Attia, Khaled Mahmoud.

Additional information

Funding

This paper was not funded.