Department of Experimental and Clinical Medicine, University of Florence, Viale G.B. Morgagni 50, 50134, Firenze, Italy.
Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126, Pisa, Italy.
Biometals. 2021 Aug;34(4):867-879. doi: 10.1007/s10534-021-00313-0. Epub 2021 Apr 27.
Chloro(triethylphosphine)gold(I), (EtPAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, EtPAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether EtPAuCl 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. EtPAuCl 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 EtPAuCl (nano-EtPAuCl 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-EtPAuCl, was clearly documented. The implications of these findings are discussed.
三乙基膦氯金（I）（简称 EtPAuCl）是一种与金诺芬（AF）相关的化合物，具有非常相似的生物学和药理学特性。与 AF 类似，EtPAuCl 在体外对多种癌细胞系表现出很强的抗增殖作用，是一种很有前途的抗癌药物候选物。我们想知道，考虑到可能减少导致不良反应和药物失活的不必要的副反应，将 EtPAuCl 包封是否会导致改善的药理学特性。EtPAuCl 被包裹在生物相容性的 PLGA-PEG 纳米颗粒（NPs）中，并与游离金复合物进行比较，在结直肠 HCT-116 癌细胞中评估新配方。值得注意的是，包裹的 EtPAuCl（简称 nano-EtPAuCl）主要保留了游离金复合物的细胞特性，并通过细胞凋亡和自噬在结直肠癌（CRC）细胞中引发更大的细胞毒性作用。此外，nano-EtPAuCl 明显抑制了两条关键信号通路，即 ERK 和 AKT。这些发现的意义将在讨论中进行探讨。
