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

doi:10.1007/s10534-021-00313-0

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

Biometals. 2021 Aug;34(4):867-879. doi: 10.1007/s10534-021-00313-0. Epub 2021 Apr 27.

Authors

Affiliations

¹ Department of Experimental and Clinical Medicine, University of Florence, Viale G.B. Morgagni 50, 50134, Firenze, Italy.
² Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126, Pisa, Italy. tiziano.marzo@unipi.it.
³ Laboratory of Metals in Medicine (MetMed), Department of Chemistry "U. Schiff", University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy.
⁴ Department of Chemistry and Industrial Chemistry (DCCI), University of Pisa, Via G. Moruzzi 13, 56124, Pisa, Italy.
⁵ Azienda Ospedaliero-Universitaria Careggi, S.C. Oncologia Medica 1, Florence, Italy.
⁶ Department of Experimental and Clinical Medicine, University of Florence, Viale G.B. Morgagni 50, 50134, Firenze, Italy. serena.pillozzi@unifi.it.
⁷ DI.V.A.L Toscana S.R.L., Via Madonna del Piano, 6, 50019, Sesto Fiorentino, Italy. serena.pillozzi@unifi.it.
⁸ Department of Chemistry and Industrial Chemistry (DCCI), University of Pisa, Via G. Moruzzi 13, 56124, Pisa, Italy. damiano.cirri@dcci.unipi.it.

^# Contributed equally.

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.

Keywords: Anticancer complexes; Auranofin; Colorectal cancer; PLGA–PEG nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Capsules
Cell Cycle / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / pathology
Drug Screening Assays, Antitumor
Humans
Nanoparticles / chemistry*
Organogold Compounds / chemical synthesis
Organogold Compounds / chemistry
Organogold Compounds / pharmacology*
Polyesters / chemistry*
Polyethylene Glycols / chemistry*
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Capsules
Organogold Compounds
Polyesters
chloro(triethylphosphine)gold(I)
polyethylene glycol-poly(lactide-co-glycolide)
Polyethylene Glycols