Transient coating of γ-Fe2O3 nanoparticles with glutamate for its delivery to and removal from brain nerve terminals.

Konstantin Paliienko,Tatiana Borisova,Artem Pastukhov,Olga Vasylchenko,Daniel Horák,Michal Babič

doi:10.3762/bjnano.11.122

Abstract

Glutamate is the main excitatory neurotransmitter in the central nervous system and excessive extracellular glutamate concentration is a characteristic feature of stroke, brain trauma, and epilepsy. Also, glutamate is a potential tumor growth factor. Using radiolabeled ʟ-[14C]glutamate and magnetic fields, we developed an approach for monitoring the biomolecular coating (biocoating) with glutamate of the surface of maghemite (γ-Fe2O3) nanoparticles. The nanoparticles decreased the initial rate of ʟ-[14C]glutamate uptake, and increased the ambient level of ʟ-[14C]glutamate in isolated cortex nerve terminals (synaptosomes). The nanoparticles exhibit a high capability to adsorb glutamate/ʟ-[14C]glutamate in water. Some components of the incubation medium of nerve terminals, that is, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and NaH2PO4, decreased the ability of γ-Fe2O3 nanoparticles to form a glutamate biocoating by about 50% and 90%, respectively. Only 15% of the amount of glutamate biocoating obtained in water was obtained in blood plasma. Albumin did not prevent the formation of a glutamate biocoating. It was shown that the glutamate biocoating is a temporal dynamic structure at the surface of γ-Fe2O3 nanoparticles. Also, components of the nerve terminal incubation medium and physiological fluids responsible for the desorption of glutamate were identified. Glutamate-coated γ-Fe2O3 nanoparticles can be used for glutamate delivery to the nervous system or for glutamate adsorption (but with lower effectiveness) in stroke, brain trauma, epilepsy, and cancer treatment following by its subsequent removal using a magnetic field. γ-Fe2O3 nanoparticles with transient glutamate biocoating can be useful for multifunctional theranostics.

Highlights

Glutamate is a main fast excitatory neurotransmitter in the central nervous system
Using radiolabeled ʟ-[14C]glutamate and liquid scintillation counting, a methodological approach was developed for a direct monitoring of the glutamate biocoating at the surface of γ-Fe2O3 nanoparticles
This study demonstrated that glutamate biocoating is a temporal dynamic structure at the surface of γ-Fe2O3 nanoparticles

Summary

Introduction

Glutamate is a main fast excitatory neurotransmitter in the central nervous system. Normal brain function in a majority of its aspects involves glutamate signaling. The extracellular glutamate level is low between episodes of exocytotic release under normal physiological conditions, thereby preventing continual activation of glutamate receptors and protecting neurons from. Each synapse presumably has a definite individual glutamate concentration in the synaptic cleft, which varies between 1 and 20 μM under normal physiological conditions depending on the method of measurements [1,2]. Glutamate uptake by the neurons and glial cells via high-affinity plasma membrane Na+-dependent glutamate transporters is responsible for the maintenance of the extracellular glutamate concentration. The transporters use Na+/K+ electrochemical gradients across the plasma membrane to accomplish glutamate transport

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