Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance.
Open accessAbstract
PURPOSE: It has been proposed in the literature that Fe(3)O(4) 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 Fe(3)O(4) 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 (EC(25) 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 (EC(25) 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.
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Iron oxide nanoparticles apply magnetic tensile forces to cause SH-SY5Y and primary Schwann cell cultures to migrate toward predefined directions.
“Apply magnetic tensile forces to cause SH-SY5Y and primary Schwann cell cultures to migrate toward predefined directions”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Riggio et al., 2012
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- Authors
- Raffa, V., Riggio, C., Calatayud, Hoskins, Pinkernelle, Goya, Wang, L., Keilhoff, & Cuschieri, A.
- Affiliations
- University of Pisa (IT)
- Scuola Superiore Sant'Anna (IT)
- University of Dundee (GB)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Universidad de Zaragoza (ES)
- Corresponding author
- Raffa, Vittoria
- Venue
- International Journal of Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2012-06
- Volume
- 7
- Pages
- 3155
- ISSN
- 1176-9114 (ISSN-L)
- 1178-2013
- PMC
- PMC3394465
- OpenAlex
- W2003800435
- Cited by
- 83
- References
- 30
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 12 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 7 · 2013: 4 · 2012: 4
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Nanomedicine (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- Ministerio de Ciencia e Innovación
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- magnetic nanoparticles, poly-L-lysine coating, Fe3O4 nanoparticles, magnetite, axon guidance, cell migration, magnetic actuation, Schwann cells, SH-SY5Y cells, oxidative stress, cytotoxicity, iron absorption, nerve regeneration, peripheral nervous system, reactive oxygen species
- MeSH terms
- Analysis of Variance, Animals, Cell Membrane, Cell Movement, Cell Survival, Cells, Cultured, Humans, Iron, Neuroblastoma, Neurons, Particle Size, Polylysine, Schwann Cells, Cell Line, Tumor, Rats, Static Electricity, Magnetite Nanoparticles
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