Synthesis and Characterization of Graphene Oxide/Polyethylene Glycol/Folic Acid/Brucine Nanocomposites and Their Anticancer Activity on HepG2 Cells

Int J Nanomedicine. 2024 Feb 5:19:1109-1124. doi: 10.2147/IJN.S445206. eCollection 2024.

Abstract

Background: Liver cancer is the sixth most prevalent form of cancer and the second major cause of cancer-associated mortalities worldwide. Cancer nanotechnology has the ability to fundamentally alter cancer treatment, diagnosis, and detection.

Objective: In this study, we explained the development of graphene oxide/polyethylene glycol/folic acid/brucine nanocomposites (GO/PEG/Bru-FA NCs) and evaluated their antimicrobial and anticancer effect on the liver cancer HepG2 cells.

Methodology: The GO/PEG/Bru-FA NCs were prepared using the co-precipitation technique and characterized using various techniques. The cytotoxicity of the GO/PEG/Bru-FA NCs was tested against both liver cancer HepG2 and non-malignant Vero cells using an MTT assay. The antimicrobial activity of the GO/PEG/Bru-FA NCs was tested against several pathogens using the well diffusion technique. The effects of GO/PEG/Bru-FA NCs on endogenous ROS accumulation, apoptosis, and MMP levels were examined using corresponding fluorescent staining assays, respectively. The apoptotic protein expressions, such as Bax, Bcl-2, and caspases, were studied using the corresponding kits.

Results: The findings of various characterization assays revealed the development of GO/PEG/Bru-FA NCs with face-centered spherical morphology and an agglomerated appearance with an average size of 197.40 nm. The GO/PEG/Bru-FA NCs treatment remarkably inhibited the growth of the tested pathogens. The findings of the MTT assay evidenced that the GO/PEG/Bru-FA NCs effectively reduced the HepG2 cell growth while not showing toxicity to the Vero cells. The findings of the fluorescent assay proved that the GO/PEG/Bru-FA NCs increased ROS generation, reduced MMP levels, and promoted apoptosis in the HepG2 cells. The levels of Bax, caspase-9, and -3 were increased, and Bcl-2 was reduced in the GO/PEG/Bru-FA NCs-treated HepG2 cells.

Conclusion: The results of this work demonstrate that GO/PEG/Bru-FA NCs suppress viability and induce apoptosis in HepG2 cells, indicating their potential as an anticancer candidate.

Keywords: apoptosis; brucine; caspases; graphene oxide; nanomedicine; photoluminescence.

MeSH terms

  • Animals
  • Anti-Infective Agents*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Folic Acid / metabolism
  • Graphite*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms* / drug therapy
  • Nanocomposites*
  • Polyethylene Glycols
  • Reactive Oxygen Species
  • Strychnine / analogs & derivatives*
  • Vero Cells
  • bcl-2-Associated X Protein

Substances

  • Polyethylene Glycols
  • graphene oxide
  • Folic Acid
  • brucine
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Anti-Infective Agents
  • Graphite
  • Strychnine