Interactions between magnetic nanowires and living cells: uptake, toxicity, and degradation

Our plain-English summary of Interactions between magnetic nanowires and living cells: uptake, toxicity, and degradation, by M. Safi, M. Yan, M.A. Guedeau-Boudeville, et al (ACS Nano, 2011).

The study

• Authors: M. Safi, M. Yan, M.A. Guedeau-Boudeville, H. Conjeaud, V. Garnier-Thibaud, N. Boggetto, A. Baeza-Squiban, F. Niedergang, D. Averbeck, J.F. Berret
• Journal: ACS Nano
• Published: 2011;5(7):5354-64
• Cited by: 70 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We report on the uptake, toxicity, and degradation of magnetic nanowires by NIH/3T3 mouse fibroblasts. Magnetic nanowires of diameters 200 nm and lengths between 1 and 40 μm are fabricated by controlled assembly of iron oxide (γ-Fe(2)O(3)) nanoparticles. Using optical and electron microscopy, we show that after 24 h incubation the wires are internalized by the cells and located either in membrane-bound compartments or dispersed in the cytosol. Using fluorescence microscopy, the membrane-bound compartments were identified as late endosomal/lysosomal endosomes labeled with lysosomal associated membrane protein (Lamp1). Toxicity assays evaluating the mitochondrial activity, cell proliferation, and production of reactive oxygen species show that the wires do not display acute short-term (<100 h) toxicity toward the cells. Interestingly, the cells are able to degrade the wires and to transform them into smaller aggregates, even in short time periods (days). This degradation is likely to occur as a consequence of the internal structure of the wires, which is that of a noncovalently bound aggregate. We anticipate that this degradation should prevent long-term asbestos-like toxicity effects related to high aspect ratio morphologies and that these wires represent a promising class of nanomaterials for cell manipulation and microrheology.

In plain English

This laboratory study looked at how mouse connective-tissue cells (NIH/3T3 fibroblasts) grown in dishes handled magnetic nanowires built from tiny iron oxide (γ-Fe2O3) particles. The wires were 200 nm wide and 1 to 40 μm long. No asbestos was tested. After 24 hours the cells had taken wires inside. From a batch with a median length of 15.6 μm, the wires found inside cells had a median length of 4.3 μm. For a 4.1 μm batch, the initial and internalized length distributions were identical. For the 4 μm wires, the iron taken up was about 35% of the maximum possible. In short-term tests, cell growth and a test of mitochondrial activity (MTT) appeared normal. In a 4-hour test, 1% to 1.8% of cells showed a reactive oxygen species signal, in treated and untreated cells alike. The authors reported no significant increase. Electron microscopy showed wire pieces and round clusters about 200 nm across, which the authors interpreted as the cells breaking the wires down. The authors anticipated that this breakdown should avoid a potential asbestos-like toxicity linked to long, thin shapes, but they did not test long-term effects. They said more experiments are needed on how the wires enter cells.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment
• Who was studied: NIH/3T3 fibroblast cells from mice, grown in culture in Paris laboratories
• Exposure: Superparamagnetic nanowires made from sub-10 nm iron oxide (γ-Fe2O3) nanoparticles: 200 nm in diameter and 1 to 40 μm long, in two batches (median lengths 4.1 μm and 15.6 μm). Single polymer-coated (PAA2K) iron oxide particles and uncoated particles were used for comparison. Doses were expressed as wires per cell and as iron concentration.
• Main results:
  • After 24 h, cells exposed to the 15 μm batch (initial median length 15.6 μm) contained wires with a median length of 4.3 μm, which the authors described as the cells sorting wires by length. For the 4.1 μm batch, the initial and internalized length distributions were identical.
  • For 4 μm nanowires (and for uncoated particles), the amount of iron taken up by cells rose linearly with iron concentration. It was about 35% of the maximum possible value.
  • In MTT tests of mitochondrial activity after 24 h, cell viability stayed around 100% for both the particles and the nanowires. In growth tests, 4 μm wires at 3, 30 and 60 wires per cell did not affect cell doubling times or final cell densities, and the cells grew normally over 80 h.
  • After 4 h of treatment at 20, 70 and 170 wires per cell, 1% to 1.8% of cells tested positive for reactive oxygen species (DHE-positive), in both untreated and treated cells. The authors reported that the number of ROS-producing cells did not significantly increase. In the hydrogen peroxide positive control, up to 80% of cells were positive at 2 mM.
  • Electron microscopy after 24 h at 30 wires per cell found wire pieces and dense round particle clusters about 200 nm across, in a ratio of about 2:1. About one-third of the iron oxide seen was in clusters. The authors concluded the wires were degraded by the cells.
  • Wires were found either in membrane-bound compartments or loose in the cell interior, never in the nucleus. The number of elongated Lamp1-positive (late endosome/lysosome) compartments was about 14% (stated margin 5%) of the number of internalized wires. Single coated nanoparticles, by contrast, were found only in membrane-bound compartments.
• The authors' conclusion: The authors concluded that the iron oxide nanowires showed no acute short-term toxicity and were degraded by the cells. They anticipated that, in the long term, all wires should be transformed, avoiding a potential asbestos-like toxicity related to high aspect ratio shapes. They concluded that the wires can be used safely with living cells as microtools.
• Limitations the authors state:
  • The authors stated that more experiments are needed to determine how the wires enter the cells.
  • The authors noted that wires looked shorter under electron microscopy because sample preparation (thin sectioning) cut them.
  • The authors attributed bends and kinks in wires seen in the immunofluorescence images to the fixation and labeling procedures.

Topics

Medical terms in this study, explained in our Lexicon: Fibroblast, Reactive Oxygen Species (ROS), Aspect Ratio (Length-to-diameter ratio).

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