Temozolomide, Gemcitabine, and Decitabine Hybrid Nanoconjugates: From Design to Proof-of-Concept (PoC) of Synergies toward the Understanding of Drug Impact on Human Glioblastoma Cells.
Ferdaous SahliManon CourcelleTony PalamaNadia DjakerPhilippe SavarinJolanda SpadavecchiaPublished in: Journal of medicinal chemistry (2020)
This paper emphasizes the synthesis of novel hybrid drug nanoparticles (Hyb-D-AuNPs) based on gold-temozolomide (TMZ) complexes combined with gemcitabine (GEM) and decitabine (DAC) to improve the efficiency and reduce the resistance of U87 malignant glial cells against TMZ. All products were evaluated by several spectroscopic techniques (Raman, UV-Vis) and transmission electron microscopy (TEM). Besides, for therapeutic purposes, the effect of these nanoparticles on cell proliferation and toxicity was evaluated, which clearly showed a synergic action of TMZ and GEM. Through the analysis of the exometabolome by nuclear magnetic resonance (NMR), the metabolic changes in the culture medium were measured in glial cells. Moreover, these nanoparticles are especially appropriated to the thermal destruction of cancer in the case of photothermal therapy due to their photothermal heating properties. This study presents an original chemical approach that it could play a central role in the field of nanomedicine, with novel perspectives for the development of new drugs and active targeting in glioblastoma multiforme (GBM) cancer therapy.
Keyphrases
- cancer therapy
- induced apoptosis
- magnetic resonance
- cell cycle arrest
- cell proliferation
- acute myeloid leukemia
- drug delivery
- endothelial cells
- endoplasmic reticulum stress
- cell death
- magnetic resonance imaging
- squamous cell carcinoma
- molecular docking
- electron microscopy
- high resolution
- signaling pathway
- mass spectrometry
- computed tomography
- spinal cord injury
- induced pluripotent stem cells
- walled carbon nanotubes
- molecular dynamics simulations