T. Borisova, B. Sojka, D. Kociołek, M. Banski, N. Pozdnyakova, A. Pastukhov, A. Borysov, M. Galkin, M. Dudarenko, A. Podhorodecki
Palladin Institiute of Biochemistry NAS of Ukraine;,
Keywords: rare earth doped nanocrystals, NaYF4, neuroactivity, glutamate and GABA transport, brain nerve terminals
Summary:Hydrophilic NaYF4 nanocrystals doped with Eu3+: Effects of surface functionalization on glutamate and GABA transport in brain nerve terminals T. Borisova2, B.Sojka1, D.Kociołek1, M. Banski1, N. Pozdnyakova2, A. Pastukhov2, A.Borysov2, M. Galkin2, M. Dudarenko2, A. Podhorodecki1 1 -Department of Experimental Physics, Wroclaw University of Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland – RECOOP CRRC 2- Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha str., Kiev, 01601, Ukraine; RECOOP CRRC Contact e-mail: firstname.lastname@example.org Specific rare earth doped nanocrystals (NCs), a recent class of nanoparticles with fluorescent features, have great bioanalytical potential. Neuroactive properties of NaYF4 nanocrystals doped with Eu3+ were assessed based on the analysis of their effects on glutamate- and -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 NaYF4:Eu-PEG and NaYF4:Eu-OH within the concentration range of 0.5-3.5 mg/ml and 0.5-1.5 mg/ml, respectively, did not influence Na+-dependent transporter-dependent L-[14C]glutamate and [3H]GABA uptake and the ambient level of the neurotransmitters in the synaptosomes. An increase in NaYF4:Eu-PEG and NaYF4:Eu-OH concentrations up to 7.5 mg/ml and 3.5 mg/ml, respectively, led to: (1) attenuation of the initial velocity of uptake of L-[14C]glutamate and [3H]GABA; (2) elevation of ambient L-[14C]glutamate and [3H]GABA in the suspension of nerve terminals. NaYF4:Eu-PEG and NaYF4:Eu-OH at concentrations of 7.5 mg/ml and 3.5 mg/ml, respectively, 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. The results of the NCs-induced changes in transport of the neurotransmitters in the synaptosomes compared to the results of carbon dots, detonation nanodiamonds, and an iron storage protein ferritin using the same methods and the neuroactivity of those nanoparticles were at concentrations of 0.08 mg/ml, 0.5 mg/ml, and 0.08 mg/ml, respectively, therefore, NCs can be considered lesser neurotoxic. Based on the unique optical properties, these NCs are good candidates for biosensing, in vitro and in vivo biomedical imaging, and after thorough preclinical testing for clinical use. In vivo applications it is necessary to control and monitor the NCs concentrations therefore the next step of the study will be the evaluation of neuroactivity at lower NCs concentrations shown in this investigation, because the NCs’ neuroactive properties could be used in the treatment of neurodegenerative diseases and in neurotheranostics. Acknowledgements: The study was supported by International Research and Innovation in Medicine Program of Cedars Sinai Medical Center, the RECOOP HST Association (Association for Regional Cooperation in the Fields of Health, Science and Technology) and the participating Cedars – Sinai Medical Center – RECOOP Research Centers (CRRC).