Neuronal cells loaded with PEI-coated Fe₃O₄ nanoparticles for magnetically guided nerve regeneration

TY - JOUR

T1 - Neuronal cells loaded with PEI-coated Fe3O4 nanoparticles for magnetically guided nerve regeneration

AU - Calatayud, M. Pilar

AU - Riggio, Cristina

AU - Raffa, Vittoria

AU - Sanz, Beatriz

AU - Torres, Teobaldo E.

AU - Ricardo Ibarra, M.

AU - Hoskins, Clare

AU - Cuschieri, Alfred

AU - Wang, Lijun

AU - Pinkernelle, Josephine

AU - Keilhofff, Gerburg

AU - Goya, Gerardo F.

PY - 2013/8/7

Y1 - 2013/8/7

N2 - We report a one-step synthesis protocol for obtaining polymer-coated magnetic nanoparticles (MNPs) engineered for uploading neural cells. Polyethyleneimine-coated Fe3O4 nanoparticles (PEI-MNPs) with sizes of 25 +/- 5 nm were prepared by oxidation of Fe(OH)(2) by nitrate in basic aqueous media and adding PEI in situ during synthesis. The obtained PEI-MNP cores displayed a neat octahedral morphology and high crystallinity. The resulting nanoparticles were coated with a thin polymer layer of about 0.7-0.9 nm, and displayed a saturation magnetization value M-S = 58 A m(2) kg(-1) at 250 K (64 A m(2) kg(-1) for T 10 K). Cell uptake experiments on a neuroblastoma-derived SH-SY5Y cell line were undertaken over a wide time and MNP concentration range. The results showed a small decrease in cell viability for 24 h incubation (down to 70% viability for 100 mu g ml(-1)), increasing the toxic effects with incubation time (30% cell survival at 100 mu g ml(-1) for 7 days of incubation). On the other hand, primary neuronal cells displayed higher sensitivity to PEI-MNPs, with a cell viability reduction of 44% of the control cells after 3 days of incubation with 50 mu g ml(-1). The amount of PEI-MNPs uploaded by SH-SY5Y cells was found to have a linear dependence on concentration. The intracellular distribution of the PEI-MNPs analyzed at the single-cell level by the dual-beam (FIB/SEM) technique revealed the coexistence of both fully incorporated PEI-MNPs and partially internalized PEI-MNP-clusters crossing the cell membrane. The resulting MNP-cluster distributions open the possibility of using these PEI-MNPs for magnetically driven axonal re-growth in neural cells.

AB - We report a one-step synthesis protocol for obtaining polymer-coated magnetic nanoparticles (MNPs) engineered for uploading neural cells. Polyethyleneimine-coated Fe3O4 nanoparticles (PEI-MNPs) with sizes of 25 +/- 5 nm were prepared by oxidation of Fe(OH)(2) by nitrate in basic aqueous media and adding PEI in situ during synthesis. The obtained PEI-MNP cores displayed a neat octahedral morphology and high crystallinity. The resulting nanoparticles were coated with a thin polymer layer of about 0.7-0.9 nm, and displayed a saturation magnetization value M-S = 58 A m(2) kg(-1) at 250 K (64 A m(2) kg(-1) for T 10 K). Cell uptake experiments on a neuroblastoma-derived SH-SY5Y cell line were undertaken over a wide time and MNP concentration range. The results showed a small decrease in cell viability for 24 h incubation (down to 70% viability for 100 mu g ml(-1)), increasing the toxic effects with incubation time (30% cell survival at 100 mu g ml(-1) for 7 days of incubation). On the other hand, primary neuronal cells displayed higher sensitivity to PEI-MNPs, with a cell viability reduction of 44% of the control cells after 3 days of incubation with 50 mu g ml(-1). The amount of PEI-MNPs uploaded by SH-SY5Y cells was found to have a linear dependence on concentration. The intracellular distribution of the PEI-MNPs analyzed at the single-cell level by the dual-beam (FIB/SEM) technique revealed the coexistence of both fully incorporated PEI-MNPs and partially internalized PEI-MNP-clusters crossing the cell membrane. The resulting MNP-cluster distributions open the possibility of using these PEI-MNPs for magnetically driven axonal re-growth in neural cells.

KW - DRUG

KW - ENHANCEMENT

KW - IRON-OXIDES

KW - CYTOTOXICITY

KW - PARTICLE-SIZE

KW - DELIVERY

U2 - 10.1039/c3tb20336k

DO - 10.1039/c3tb20336k

M3 - Article

SN - 2050-750X

VL - 1

SP - 3607

EP - 3616

JO - Journal of Materials Chemistry B: Materials for Biology and Medicine

JF - Journal of Materials Chemistry B: Materials for Biology and Medicine

IS - 29

ER -