Effects of surface functionalization of hydrophilic NaYF(4) nanocrystals doped with Eu(3+) on glutamate and GABA transport in brain synaptosomes

Specific rare earth doped nanocrystals (NCs), a recent class of nanoparticles with fluorescent features, have great bioanalytical potential. Neuroactive properties of NaYF(4) nanocrystals doped with Eu(3+) were assessed based on the analysis of their effects on glutamate- and γ-aminobutyric acid (GABA) transport process in nerve terminals isolated from rat brain (synaptosomes). Two types of hydrophilic NCs were examined in this work: (i) coated by polyethylene glycol (PEG) and (ii) with OH groups at the surface. It was found that NaYF(4):Eu(3+)-PEG and NaYF(4):Eu(3+)-OH within the concentration range of 0.5–3.5 and 0.5–1.5 mg/ml, respectively, did not influence Na(+)-dependent transporter-dependent l-[(14)C]glutamate and [(3)H]GABA uptake and the ambient level of the neurotransmitters in the synaptosomes. An increase in NaYF(4):Eu(3+)-PEG and NaYF(4):Eu(3+)-OH concentrations up to 7.5 and 3.5 mg/ml, respectively, led to the (1) attenuation of the initial velocity of uptake of l-[(14)C]glutamate and [(3)H]GABA and (2) elevation of ambient neurotransmitters in the suspension of nerve terminals. In the mentioned concentrations, nanocrystals did not influence acidification of synaptic vesicles that was shown with pH-sensitive fluorescent dye acridine orange, however, decreased the potential of the plasma membrane of synaptosomes. In comparison with other nanoparticles studied with similar methodological approach, NCs start to exhibit their effects on neurotransmitter transport at concentrations several times higher than those shown for carbon dots, detonation nanodiamonds and an iron storage protein ferritin, whose activity can be registered at 0.08, 0.5 and 0.08 mg/ml, respectively. Therefore, NCs can be considered lesser neurotoxic as compared to above nanoparticles.