Nanoscale metal oxides and lung cells

Bear in mind while reading further that all of this research has not taken place in any situation resembling real life conditions: researchers at the Missouri University of Science and Technology (Missouri S&T; located in the US) have found that metal oxides at the nanoscale can be highly toxic to human lung cells according to a Jan. 28, 2014 news item on Nanowerk (Note: A link has been removed),

Nanoparticles are used in all kinds of applications — electronics, medicine, cosmetics, even environmental clean-ups. More than 2,800 commercially available applications are now based on nanoparticles, and by 2017, the field is expected to bring in nearly $50 billion worldwide.

But this influx of nanotechnology is not without risks, say researchers at Missouri University of Science and Technology.

“There is an urgent need to investigate the potential impact of nanoparticles on health and the environment,” says Yue-Wern Huang, professor of biological sciences at Missouri S&T.

Huang and his colleagues have been systematically studying the effects of transition metal oxide nanoparticles on human lung cells (“Cytotoxicity in the age of nano: The role of fourth period transition metal oxide nanoparticle physicochemical properties”). These nanoparticles are used extensively in optical and recording devices, water purification systems, cosmetics and skin care products, and targeted drug delivery, among other applications.

The Jan. 27, 2014 Missouri S&T news release by Linda Fulps, which originated the news item, describes the research in more detail,

“In their typical coarse powder form, the toxicity of these substances is not dramatic,” says Huang. “But as nanoparticles with diameters of only 16-80 nanometers, the situation changes significantly.”

The researchers exposed both healthy and cancerous human lung cells to nanoparticles composed of titanium, chromium, manganese, iron, nickel, copper and zinc compounds — transition metal oxides that are on the fourth row of the periodic table. The researchers discovered that the nanoparticles’ toxicity to the cells, or cytotoxicity, increased as they moved right on the periodic table.

“About 80 percent of the cells died in the presence of nanoparticles of copper oxide and zinc oxide,” says Huang. “These nanoparticles penetrated the cells and destroyed their membranes. The toxic effects are related to the nanoparticles’ surface electrical charge and available docking sites.”

Huang says that certain nanoparticles released metal ions — called ion dissolution — which also played a significant role in cell death.

Huang is now working on new research that may help reduce nanoparticles’ toxicity and shed light on how nanoparticles interact with cells.

“We are coating toxic zinc oxide nanoparticles with non-toxic nanoparticles to see if zinc oxide’s toxicity can be reduced,” Huang says. “We hope this can mitigate toxicity without compromising zinc oxide’s intended applications. We’re also investigating whether nanoparticles inhibit cell division and influence cell cycle.”

Concerning results? Yes. But, before determining how alarmed you should be, there are a few questions you might want to ask while reading the news release and/or the research paper :

  1. How were these cells exposed to the metal nanoparticles? ‘Breathing’ or were they sitting in a solution?
  2. What was the concentration of metal nanoparticles? (even good things can be bad for you at high concentrations)

This isn’t an attempt to dismiss the findings but rather to point out how much painstaking research has to take place before conclusions of any kind can be drawn. It’s why scientists tend to quite careful in their comments.

In looking at this work, I was reminded of the research into ‘nanosunscreens’ and concerns about the metal oxide nanoparticles (zinc oxides and/or titanium dioxide) penetrating the skin barrier and building up to toxic levels in the body.  In an Oct. 4, 2012 posting about zinc oxide nanoparticles and penetrating the skin barrier, I mentioned this in the context of some then recent research at Bath University (UK),

I missed the fact that this study was an in vitro test, which is always less convincing than in vivo testing. In my Nov. 29, 2011 posting about some research into nano zinc oxide I mentioned in vitro vs. in vivo testing and Brian Gulson’s research,

I was able to access the study and while I’m not an expert by any means I did note that the study was ‘in vitro’, in this case, the cells were on slides when they were being studied. It’s impossible to draw hard and fast conclusions about what will happen in a body (human or otherwise) since there are other systems at work which are not present on a slide.

… here’s what Brian Gulson had to say about nano zinc oxide concentrations in his work and about a shortcoming in his study (from an Australian Broadcasting Corporation [ABC] Feb. 25, 2010 interview with Ashley Hall,

BRIAN GULSON: I guess the critical thing was that we didn’t find large amounts of it getting through the skin. The sunscreens contain 18 to 20 per cent zinc oxide usually and ours was about 20 per zinc. So that’s an awful lot of zinc you’re putting on the skin but we found tiny amounts in the blood of that tracer that we used.

ASHLEY HALL: So is it a significant amount?

BRIAN GULSON: No, no it’s really not.

ASHLEY HALL: But Brian Gulson is warning people who use a lot of sunscreen over an extended period that they could be at risk of having elevated levels of zinc.

BRIAN GULSON: Maybe with young children where you’re applying it seven days a week, it could be an issue but I’m more than happy to continue applying it to my grandchildren.

ASHLEY HALL: This study doesn’t shed any light on the question of whether the nano-particles themselves played a part in the zinc absorption.

BRIAN GULSON: That was the most critical thing. This isotope technique cannot tell whether or not it’s a zinc oxide nano-particle that got through skin or whether it’s just zinc that was dissolved up in contact with the skin and then forms zinc ions or so-called soluble ions. So that’s one major deficiency of our study.

Of course, I have a question about Gulson’s conclusion  that very little of the nano zinc oxide was penetrating the skin based on blood and urine samples taken over the course of the study. Is it possible that after penetrating the skin it was stored in the cells  instead of being eliminated?

Here’s a link to and a citation for Yue-Wern Huang and his team’s latest research,

Cytotoxicity in the age of nano: The role of fourth period transition metal oxide nanoparticle physicochemical properties by Charles C. Chusuei, Chi-Heng Wu, Shravan Mallavarapu, Fang Yao Stephen Hou, Chen-Ming Hsu, Jeffrey G. Winiarz, Robert S. Aronstam, Yue-Wern Huang. Chemico-Biological Interactions, Volume 206, Issue 2, 25 November 2013, Pages 319–326.

This paper is behind a paywall.

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