There are many potential applications of gold nanoparticles in medicine. Gold nanoparticles are already being used in diagnostics, as in pregnancy or HIV tests . Research on the use as a contrast agent for the localization of cancer cells and as a drug delivery system for targeted release at site of action. The surface properties of gold are optimal for functionalization, e.g. with chitosan.
Chitosan gold nanoparticles induce different ROS-dependent cell death modalities in leukemic cells
Ana Carolina Martínez-Torres, Helen Yarimet, Lorenzo-Anota, Martín Gerardo, García-Juárez, Diana G Zarate-Triviño, Cristina Rodríguez-Padilla, Int J Nanomedicine. 2019; 14: 7173–7190. Published online 2019 Sep 4. doi: 10.2147/IJN.S221021
Gold nanoparticles have been studied to treat a wide variety of diseases, including multiple cancer types. In this study from Mexico, researchers investigated the potential of using chitosan functionalized gold nanoparticles to treat leukemia. In patients with leukemia, white blood cells are affected. It can be distinguished between acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML). Mutations or deletions in proteins involved in regulated cell death cause resistance to conventional treatments, such as chemotherapy. In previous experiments, researchers demonstrated that chitosan-coated gold nanoparticles induce cell death in HeLa and MCF-7 cancer cells without affecting peripheral blood mononuclear cells (PBMC), such as lymphocytes and monocytes.
In the study, it was investigated whether the selectivity of the chitosan-coated gold nanoparticles is due to the cell line or the properties of the cancer cells. Cell death mechanisms, the effects of nuclear damage and autophagosome formation have also been investigated. Gold nanoparticles were coated with chitosan (medium molecular weight, 75-85% of deacetylation). These were tested on T-acute lymphocytic leukemia cell lines (CEM), in a chronic myeloid leukemia cell line (K562) and in healthy cells of the same line (PBMC and bone marrow). The study investigated ROS generation (reactive oxygen species) and the formation of mitochondrial and nuclear damage. It was also tested whether the cell death was triggered by autophagy, apoptosis or necroptosis and the role of oxygen radicals in these mechanisms.
- Chitosan-coated gold nanoparticles
- have a toxic effect on leukemia cells (dose-dependent)
- have no effect on PBMC and bone marrow cells
- induce apoptosis in CEM and necroptosis in K562 cells (cells survive through autophagy processes)
Conclusion: The study showed that chitosan-coated gold nanoparticles induce cell death of leukemia cells in vitro without affecting healthy cells. However, the mechanism of cell death depends on the type of leukemia cell.
Gold nanoparticles with chitosan, N-acylated chitosan, and chitosan oligosaccharide as DNA carriers.
Abrica-González, Zamora-Justo, Sotelo-López, Vázquez-Martínez, Balderas-López, Muñoz-Diosdado, Ibáñez-Hernández. Nanoscale Res Lett. 2019 Jul 30; 14(1):258. doi: 10.1186/s11671-019-3083-y
In the second study, routes of synthesis were investigated to functionalize gold nanoparticles with chitosan. One application of these functionalized nanoparticles could be gene therapy, where genetic material is introduced directly into the cells, for the treatment of genetic diseases. The authors developed gold nanoparticles functionalized with chitosan, acetylated chitosan, and chitosan oligosaccharides and loaded with plasmid DNA. For this, two different ways of synthesis were used. For the functionalization with chitosan or acetylated chitosan, the toxic reducing agent sodium borohydride was used. In a one-pot synthesis, chitosan oligosaccharide itself acted as a reducing and stabilizing agent. Transfection efficiency of the prepared nanoparticles with plasmid DNA was tested in vitro (HEK-293 cells).
- good stability of functionalized nanoparticles
- gold nanoparticles with chitosan oligosaccharides were synthesized without the use of toxic chemicals ("green" technology/one-pot synthesis)
- Successful incorporation of plasmid DNA by the nanoparticles through interaction with the positively charged chitosans
- transfection rates of functionalized gold nanoparticles with plasmid DNA were 27% (chitosan), 33% (N-acetyl chitosan) and 60% (chitosan oligosaccharide)
Conclusion: The functionalization of gold nanoparticles with chitosan oligosaccharides is possible without the use of toxic chemicals. These Nanoparticles also had the highest transfection efficiency compared to the chemically synthesized gold nanoparticles functionalized with chitosan and N-acetylated chitosan.