Anticancer effects against colorectal cancer models of chloro(triethylphosphine)gold(I) encapsulated in PLGA–PEG nanoparticles
Alessio Menconi, Tiziano Marzo, Lara Massai, Alessandro Pratesi, Mirko Severi, Giulia Petroni, Lorenzo Antonuzzo, Luigi Messori, Serena Pillozzi, Damiano Cirri
Abstract
Abstract Chloro(triethylphosphine)gold(I), (Et 3 PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et 3 PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et 3 PAuCl 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. Et 3 PAuCl 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 Et 3 PAuCl (nano-Et 3 PAuCl 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-Et 3 PAuCl, was clearly documented. The implications of these findings are discussed.