Anticancer effects against colorectal cancer models of chloro(triethylphosphine)gold(I) encapsulated in PLGA\u2013PEG nanoparticles

Alessio Menconi,Tiziano Marzo,Alessandro Pratesi,Lorenzo Antonuzzo,Luigi Messori,Lara Massai,Damiano Cirri,Serena Pillozzi,Mirko Severi,Giulia Petroni

doi:10.1007/s10534-021-00313-0

Alessio Menconi, Tiziano Marzo + Show 8 more

Open Access

https://doi.org/10.1007/s10534-021-00313-0

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Abstract

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.

Highlights

Auranofin (AF) is an established gold(I) drug for the treatment of rheumatoid arthritis, in clinical use since 1986 (Bombardier et al 1986)
A quite homogeneous monodispersed preparation of PLGA–PEG nanoparticles was obtained with an average size of 65 nm (Table S1 supporting material)
We wondered whether a nanoformulation of Et3PAuCl, in particular its encapsulation into PLGA–PEG nanoparticles, might result into improved pharmacological and anticancer performances

Summary

Introduction

Auranofin (AF) is an established gold(I) drug for the treatment of rheumatoid arthritis, in clinical use since 1986 (Bombardier et al 1986). (Pratesi et al 2018; Zoppi et al 2020) while the thiosugar moiety mainly acts as a carrier ligand improving the bioavailability and the gold complex pharmacokinetic profile when orally administered (Marzo et al 2017). Based on these arguments, recently, we started a systematic and comparative evaluation of a series of AF-related compounds (Marzo et al 2017, 2018; Tolbatov et al 2020). The Au centre can react with sulphur-containing solvent exposed aminoacidic residues of serum proteins (Zoppi et al 2020)

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