Anticancer effects against colorectal cancer models of chloro(triethylphosphine)gold(I) encapsulated in PLGA-PEG nanoparticles.
Alessio MenconiTiziano MarzoLara MassaiAlessandro PratesiMirko SeveriGiulia PetroniLorenzo AntonuzzoLuigi MessoriSerena PillozziDamiano CirriPublished in: Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine (2021)
Chloro(triethylphosphine)gold(I), (Et3PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et3PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et3PAuCl encapsulation might lead to an improved pharmacological profile also considering the likely reduction of unwanted side-reactions that are responsible for adverse effects and for drug inactivation. Et3PAuCl was encapsulated in biocompatible PLGA-PEG nanoparticles (NPs) and the new formulation evaluated in colorectal HCT-116 cancer cells in comparison to the free gold complex. Notably, encapsulated Et3PAuCl (nano-Et3PAuCl hereafter) mostly retains the cellular properties of the free gold complex and elicits even greater cytotoxic effects in colorectal cancer (CRC) cells, mediated by apoptosis and autophagy. Moreover, a remarkable inhibition of two crucial signaling pathways, i.e. ERK and AKT, by nano-Et3PAuCl, was clearly documented. The implications of these findings are discussed.
Keyphrases
- signaling pathway
- cell cycle arrest
- drug delivery
- pi k akt
- induced apoptosis
- cell death
- endoplasmic reticulum stress
- oxidative stress
- drug release
- atrial fibrillation
- cell proliferation
- silver nanoparticles
- epithelial mesenchymal transition
- papillary thyroid
- emergency department
- ionic liquid
- young adults
- anti inflammatory
- bone regeneration
- lymph node metastasis