Unique features of brain metastases-targeted AGuIX nanoparticles vs their constituents: A focus on glutamate-/GABA-ergic neurotransmission in cortex nerve terminals

被引：8

作者：

Borisova, Tatiana ^{[1
]}

Pozdnyakova, Natalia ^{[1
]}

Krisanova, Natalia ^{[1
]}

Pastukhov, Artem ^{[1
]}

Dudarenko, Marina ^{[1
]}

Paliienko, Konstantin ^{[1
]}

Grytsaenko, Valeria ^{[1
]}

Lux, Francois ^{[2
]}

Lysenko, Vladimir ^{[2
]}

Rocchi, Paul ^{[2
]}

Komisarenko, Serhiy ^{[1
]}

Tillement, Olivier ^{[2
]}

机构：

[1] Natl Acad Sci Ukraine, Palladin Inst Biochem, 9 Leontovicha St, UA-01054 Kiev, Ukraine

[2] Claude Bernard Univ Lyon, Univ Lyon, Light Matter Inst, UMR 5306,CNRS, F-69622 Villeurbanne, France

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2021年 / 149卷

基金：

新加坡国家研究基金会;

关键词：

AGuIX nanoparticles; DOTAGA; Gd3+; Exocytosis; Transporters; Neurotransmitter release; Glutamate; GABA; Presynaptic nerve terminals; Neurotoxicity risk assessment; GADOLINIUM-BASED NANOPARTICLES; TRANSPORT; PLANETARY; ANIMALS;

D O I：

10.1016/j.fct.2021.112004

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

Gadolinium-based radiosensitizing AGuIX nanoparticles (AGuIX) currently tested two phase 2 clinical trials in association with radiotherapy for the treatment of brain metastases. Here, excitatory/inhibitory neurotransmission was assessed in rat cortex nerve terminals in the presence of AGuIX and their constituents (DOTAGA and DOTAGA/Gd3+) at concentrations used for medical treatment, and those 5-24 times higher. The ambient level, transporter-mediated, tonic and exocytotic release of L-[C-14]glutamate and [H-3]GABA, the membrane potential of nerve terminals were not changed in the presence of AGuIX at concentrations used for medical treatment ([Gd3+] = 0.25 mM, corresponding to 0.25 g.L-1), and DOTAGA (0.25 mM) and DOTAGA/Gd3+ (0.25 mM/0.01 mM). Difference between AGuIX and the precursors was uncovered, when their concentrations were increased. AGuIX (1.25-6 mM) did not change any transport characteristics of L-[C-14]glutamate and [H-3]GABA, whereas, DOTAGA (1.25-6 mM) affected the membrane potential, ambient level, and exocytotic release of L-[C-14] glutamate and [H-3]GABA. Gd3+ did not mask, but even enhanced above effects of DOTAGA. Therefore, AGuIX did not influence glutamate- and GABA-ergic neurotransmission at the presynaptic site. In contrast, DOTAGA and mixture DOTAGA/Gd3+ significantly affected synaptic neurotransmission at high concentrations. AGuIX own structure that overcomes neurotoxic features of their constituents.

引用

页数：12