Back to Browse Journals » International Journal of Nanomedicine » Volume 7

Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

Authors Riggio C, Calatayud MP, Hoskins C, Pinkernelle J, Sanz B, Torres TE, Ibarra MR, Wang L, Keilhoff G, Goya GF, Raffa V, Cuschieri A

Received 22 November 2011

Accepted for publication 3 February 2012

Published 25 June 2012 Volume 2012:7 Pages 3155—3166

DOI https://doi.org/10.2147/IJN.S28460

Review by Single-blind

Peer reviewer comments 2

Cristina Riggio,1,* Maria Pilar Calatayud,2,* Clare Hoskins,3 Josephine Pinkernelle,4 Beatriz Sanz,2 Teobaldo Enrique Torres,2,5 Manuel Ricardo Ibarra,2,5 Lijun Wang,3 Gerburg Keilhoff,4 Gerardo Fabian Goya,2,5 Vittoria Raffa,1,6 Alfred Cuschieri1,3

1Institute of Life Science, Scuola Superiore Sant’Anna, Piazza Martiri della Libertà, Pisa, Italy; 2Instituto de Nanociencia de Aragón, Universidad de Zaragoza. Mariano Esquillor, Zaragoza, Spain; 3IMSaT, Institute for Medical Science and Technology, University of Dundee, Dundee, Scotland; 4Otto-von-Guericke University, Institute of Biochemistry and Cell Biology, Magdeburg, Germany; 5Departamento de Física de la Materia Condensada, Facultad de Ciencias, Universidad de Zaragoza. Cerbuna 12, Zaragoza, Spain; 6Department of Biology, Università di Pisa, Pisa, Italy

*These authors contributed equally to this work

Purpose: It has been proposed in the literature that Fe3O4 magnetic nanoparticles (MNPs) could be exploited to enhance or accelerate nerve regeneration and to provide guidance for regenerating axons. MNPs could create mechanical tension that stimulates the growth and elongation of axons. Particles suitable for this purpose should possess (1) high saturation magnetization, (2) a negligible cytotoxic profile, and (3) a high capacity to magnetize mammalian cells. Unfortunately, the materials currently available on the market do not satisfy these criteria; therefore, this work attempts to overcome these deficiencies.
Methods: Magnetite particles were synthesized by an oxidative hydrolysis method and characterized based on their external morphology and size distribution (high-resolution transmission electron microscopy [HR-TEM]) as well as their colloidal (Z potential) and magnetic properties (Superconducting QUantum Interference Devices [SQUID]). Cell viability was assessed via Trypan blue dye exclusion assay, cell doubling time, and MTT cell proliferation assay and reactive oxygen species production. Particle uptake was monitored via Prussian blue staining, intracellular iron content quantification via a ferrozine-based assay, and direct visualization by dual-beam (focused ion beam/scanning electron microscopy [FIB/SEM]) analysis. Experiments were performed on human neuroblastoma SH-SY5Y cell line and primary Schwann cell cultures of the peripheral nervous system.
Results: This paper reports on the synthesis and characterization of polymer-coated magnetic Fe3O4 nanoparticles with an average diameter of 73 ± 6 nm that are designed as magnetic actuators for neural guidance. The cells were able to incorporate quantities of iron up to 2 pg/cell. The intracellular distribution of MNPs obtained by optical and electronic microscopy showed large structures of MNPs crossing the cell membrane into the cytoplasm, thus rendering them suitable for magnetic manipulation by external magnetic fields. Specifically, migration experiments under external magnetic fields confirmed that these MNPs can effectively actuate the cells, thus inducing measurable migration towards predefined directions more effectively than commercial nanoparticles (fluidMAG-ARA supplied by Chemicell). There were no observable toxic effects from MNPs on cell viability for working concentrations of 10 µg/mL (EC25 of 20.8 µg/mL, compared to 12 µg/mL in fluidMAG-ARA). Cell proliferation assays performed with primary cell cultures of the peripheral nervous system confirmed moderate cytotoxicity (EC25 of 10.35 µg/mL).
Conclusion: These results indicate that loading neural cells with the proposed MNPs is likely to be an effective strategy for promoting non-invasive neural regeneration through cell magnetic actuation.
Keywords: magnetic nanoparticle, actuator, migration, neural regeneration

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other article by this author:

Zinc oxide nanoparticles as selective killers of proliferating cells

Taccola L, Raffa V, Riggio C, Vittorio O, Iorio MC, Vanacore R, Pietrabissa A, Cuschieri A

International Journal of Nanomedicine 2011, 6:1129-1140

Published Date: 30 May 2011

Readers of this article also read:

Heparin nanomodification improves biocompatibility and biomechanical stability of decellularized vascular scaffolds

Tao Y, Hu T, Wu Z, Tang H, Hu Y, Tan Q, Wu C

International Journal of Nanomedicine 2012, 7:5847-5858

Published Date: 26 November 2012

Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis

Yang HW, Hua MY, Lin KJ, Wey SP, Tsai RY, Wu SY, Lu YC, Liu HL, Wu T, Ma YH

International Journal of Nanomedicine 2012, 7:5159-5173

Published Date: 1 October 2012

Development of a reduction-sensitive diselenide-conjugated oligoethylenimine nanoparticulate system as a gene carrier

Cheng G, He Y, Xie L, Nie Y, He B, Zhang Z, Gu Z

International Journal of Nanomedicine 2012, 7:3991-4006

Published Date: 31 July 2012

Influence of carbon nanotube length on toxicity to zebrafish embryos

Cheng J, Cheng SH

International Journal of Nanomedicine 2012, 7:3731-3739

Published Date: 20 July 2012

Nimodipine-loaded mixed micelles: formulation, compatibility, pharmacokinetics, and vascular irritability study

Song X, Jiang Y, Ren CJ, Sun X, Zhang Q, Gong T, Zhang ZR

International Journal of Nanomedicine 2012, 7:3689-3699

Published Date: 13 July 2012

Development of 3D in vitro platform technology to engineer mesenchymal stem cells

Hosseinkhani H, Hong P, Yu D, Chen Y, Ickowicz D, Farber I, Domb AJ

International Journal of Nanomedicine 2012, 7:3035-3043

Published Date: 29 June 2012

Controlled release of 5-fluorouracil and progesterone from magnetic nanoaggregates

Ragab DM, Rohani S, Consta S

International Journal of Nanomedicine 2012, 7:3167-3189

Published Date: 29 June 2012

Comparing the effects of nano-sized sugarcane fiber with cellulose and psyllium on hepatic cellular signaling in mice

Wang ZQ, Yu Y, Zhang XH, Floyd ZE, Boudreau A, Lian K, Cefalu WT

International Journal of Nanomedicine 2012, 7:2999-3012

Published Date: 18 June 2012