A comparative study of neurotoxic potential of synthesized polysaccharide-coated and native ferritin-based magnetic nanoparticles

Abstract

AimTo analyze the neurotoxic potential of synthesized magnetite nanoparticles coated by dextran, hydroxyethyl starch, oxidized hydroxyethyl starch, and chitosan, and magnetic nanoparticles combined with ferritin as a native protein.MethodsThe size of nanoparticles was analyzed using photon correlation spectroscopy, their effects on the conductance of planar lipid membrane by planar lipid bilayer technique, membrane potential and acidification of synaptic vesicles by spectrofluorimetry, and glutamate uptake and ambient level of glutamate in isolated rat brain nerve terminals (synaptosomes) by radiolabeled assay.ResultsUncoated synthesized magnetite nanoparticles and nanoparticles coated by different polysaccharides had no significant effect on synaptic vesicle acidification, the initial velocity of L-[14C]glutamate uptake, ambient level of L-[14C]glutamate and the potential of the plasma membrane of synaptosomes, and conductance of planar lipid membrane. Native ferritin-based magnetic nanoparticles had no effect on the membrane potential but significantly reduced L-[14C]glutamate transport in synaptosomes and acidification of synaptic vesicles.ConclusionsOur study indicates that synthesized magnetite nanoparticles in contrast to ferritin have no effects on the functional state and glutamate transport of nerve terminals, and so ferritin cannot be used as a prototype, analogue, or model of polysaccharide-coated magnetic nanoparticle in toxicity risk assessment and manipulation of nerve terminals by external magnetic fields. Still, the ability of ferritin to change the functional state of nerve terminals in combination with its magnetic properties suggests its biotechnological potential.

Synthesis of new fluorinated analogs of GABA, Pregabalin bioisosteres, and their effects on [3H]GABA uptake by rat brain nerve terminals

“…All procedures conformed to the guidelines of the Palladin Institute of Biochemistry. [27][28][29] Before starting the experiments, the protocols were approved by the Animal Care and Use Committee of the Palladin Institute of Biochemistry (Protocol from 19/09-2012).…”

Effects of surface functionalization of hydrophilic NaYF4 nanocrystals doped with Eu3+ on glutamate and GABA transport in brain synaptosomes

“…Ferritin stores cellular iron in a dynamic manner, allowing the release of the metal according to demand. We found that exogenous ferritin at a concentration of 0.08 mg/ml (iron content 0.7%) demonstrated neuroactive features (Borysov et al 2014 ). The fourth type of nanoparticles included in the comparative analysis is native dust particles derived from ash deposit of fallen volcanic air (JSC-1a, and JSC, Mars-1A from ORBITEC Orbital Technologies Corporation).…”

“…Only changes in unspecific glutamate binding to synaptosomes in the presence of JSC-1a were found. Summarizing, carbon dots (Borisova et al 2015 ), detonation nanodiamonds (Pozdnyakova et al 2016 ) and physiological nanocomplex ferritin exhibited neuroactivity at concentrations of 0.08, 0.5 and 0.08 mg/ml, respectively (Borysov et al 2014 ). Whereas, the ability of NaYF 4 :Eu 3+ -PEG and NaYF 4 :Eu 3+ -OH to influence neurotransmitter transport was registered at concentrations starting from 7.5 to 3.5 mg/ml.…”

“…Recently, we have demonstrated that d -mannose-coated superparamagnetic maghemite (γ-Fe 2 O 3 ) nanoparticles (Borisova et al 2014 ) did not affect key characteristics of glutamatergic neurotransmission. In contrast, native physiologically available and synthesized in organism nanoparticles, that is, ferritin, which contains magnetic core and protein shell, affected synaptic neurotransmission (Borysov et al 2014 ).…”

New effects of GABAB receptor allosteric modulator rac-BHFF on ambient GABA, uptake/release, Em and synaptic vesicle acidification in nerve terminals

“…Membrane potential was measured using a potentiometric fluorescent dye rhodamine 6G (0.5 µM) based on its potential-mediated binding to the plasma membrane Borysov et al, 2014Kasatkina and Borisova, 2010). The suspension of synaptosomes (0.2 mg ml -1 of final protein concentration) after preincubation at 37 °C for 10 min was added to stirred thermostated cuvette.…”