Targeted delivery of bee venom to A549 lung cancer cells by PEGylate liposomal formulation: an apoptotic investigation

Sci Rep. 2024 Jul 27;14(1):17302. doi: 10.1038/s41598-024-68156-6.

Abstract

This study focused on developing an optimal formulation of liposomes loaded with bee venom (BV) and coated with PEG (BV-Lipo-PEG). The liposomes were characterized using dynamic light scattering, transmission electron microscopy, and Fourier transform infrared spectroscopy. Among the liposomal formulations, F3 exhibited the narrowest size distribution with a low PDI value of 193.72 ± 7.35, indicating minimal agglomeration-related issues and a more uniform size distribution. BV-Lipo-PEG demonstrated remarkable stability over 3 months when stored at 4 °C. Furthermore, the release of the drug from the liposomal formulations was found to be pH-dependent. Moreover, BV-Lipo-PEG exhibited favorable entrapment efficiencies, with values reaching 96.74 ± 1.49. The anticancer potential of the liposomal nanocarriers was evaluated through MTT assay, flow cytometry, cell cycle analysis, and real-time experiments. The functionalization of the liposomal system enhanced endocytosis. The IC50 value of BV-Lipo-PEG showed a notable decrease compared to both the free drug and BV-Lipo alone, signifying that BV-Lipo-PEG is more effective in inducing cell death in A549 cell lines. BV-Lipo-PEG exhibited a higher apoptotic rate in A549 cell lines compared to other samples. In A549 cell lines treated with BV-Lipo-PEG, the expression levels of MMP-2, MMP-9, and Cyclin E genes decreased, whereas the expression levels of Caspase3 and Caspase9 increased. These findings suggest that delivering BV via PEGylated liposomes holds significant promise for the treatment of lung cancer.

Keywords: Endocytosis; Liposome; Lung cancer; PEG; Venom.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis* / drug effects
  • Bee Venoms* / chemistry
  • Bee Venoms* / pharmacology
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Drug Delivery Systems
  • Drug Liberation
  • Humans
  • Liposomes* / chemistry
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Polyethylene Glycols* / chemistry

Substances

  • Bee Venoms
  • Liposomes
  • Polyethylene Glycols
  • Antineoplastic Agents
  • Caspase 9
  • Matrix Metalloproteinase 9