Nanoparticle–DNA Toxicity Finding Sparks Debate About Toxicity and Press Reporting of Science
The world of nanomedicine was thrown into a global debate last month following a study published in Nature Nanotechnology that demonstrated the ability of nanoparticles to cause damage to DNA without breaching the cellular barrier and raised questions about press reporting of scientific studies.
The study, in which a team from the University of Bristol (UK), led by Dr Charles Patrick Case, created cancerous cellular biofilm barriers and then focused a stream of cobalt–chromium nanoparticles at them, demonstrating that although the nanoparticles did not breach the barrier layers, they caused damage to cells beyond the barrier. The experiment used a specially designed cell culture and was part of a wider body of work investigating the use of cobalt–chromium nanoparticles in orthopedics.
In spite of the University of Bristol press release including a quote from Patrick Case, senior author on the study, saying: “We need to be clear that our experimental set up is not a model of the human body. The cells receiving the exposure were bathed in culture media, whilst in the body they might be separated from the barrier by connective tissue and blood vessels. The barrier cells were malignant cell line and three cells in thickness whilst all barriers in the body are less thick and of nonmalignant cells,” the team concluded their abstract by noting that “the potential damage to tissues located behind cell barriers needs to be considered when using nanoparticles for targeting disease states” and Nature Nanotechnology, the journal in which the paper will be published, wrote a press release entitled “Damaging DNA from a distance” and called a press conference to discuss the results, causing stories about potential nanoparticle toxicity problems to make headlines in the UK and world press.
The journal Science was quick to criticize Nature‘s handling of the paper, publishing an article by science writer Robert Service quoting Andre Nel from the University of California, Los Angeles (CA, USA) who said that Nature had used the kind of language that scares and confuses the public, especially when there‘s no evidence that the findings translate to people.
“I think it‘s a meaningless study, to be blunt,” commented Günter Oberdörster, from the University of Rochester in New York (USA). “We need to be much more careful in interpreting these results.”
Nature‘s blog, The Great Beyond, published an article in response citing Andrew Maynard, the Chief Science Advisor to the Project on Emerging Nanotechnologies at the Woodrow Wilson International Center for Scholars in Washington, DC, USA, who commented “It‘s an important study as it raises possible new ways in which harm could occur following exposure. But while it raises new questions, it is far from conclusive on whether this is a relevant or significant way in which specific types of nanoparticles can cause harm. More research is needed.”
Sources: Bhabra G, Sood A, Fisher B et al.: Nanoparticles can cause DNA damage across a cellular barrier. Nat. Nanotech. (2009) (Epub ahead of print); Damaging DNA from a distance. Nature Nanotechnology press release: www.nature.com/nnano/press_releases/nnano1109.html; Tiny tech sparks cell signal find. BBC news: http://news.bbc.co.uk/1/hi/sci/tech/834481.stm; Nanoparticle safety looking more complicated. Nature blog: http://blogs.nature.com/news/thegreatbeyond/2009/11/nanoparticle_safety_looking_mo.html; Experts criticize nanoparticle study. Science magazine: http://sciencenow.sciencemag.org/cgi/content/full/2009/1106/1
Magforce Nanotechnologies Announce Success of Nano-Cancer® Clinical Trial
German-based company MagForce Nanotechnologies AG announced the completion of the first trial of their Nano-Cancer® drug, which could potentially prolong the life of cancer patients.
The Nano-Cancer therapy involves an injection of coated iron oxide nanoparticles into the tumor site, followed by the application of an external magnetic field that heats the particles, and thus the tumor, to up to 70°C, damaging and destroying the tumor. The heating can be controlled to within a fraction of the degree. The therapy has no reported side effects, as the nanoparticles remain localized within the tumor.
The trial was conducted on 59 patients with brain cancer recurrent glioblastomas, who had not responded to previous conventional therapies such as chemotherapy, surgery and radiation. The results showed that patients using the therapy in conjunction with traditional radiation therapy extended their median lifespan by 7.2–13.4 months, compared with a previous study of median survival time among a large patient population.
Chief scientific officer of MagForce Nanotechnologies AG, Andreas Jordan, commented, “The results demonstrate the potential of Nano-Cancer therapy, which at the same time has minimal patient side effects. Our vision is to establish this new technology alongside surgery, chemotherapy and radiation as an additional pillar of cancer therapy.”
The company plans to use the results of the clinical trial to apply for EU regulatory approval for the therapy.
Source: MagForce Nanotechnologies press release. MagForce Nanotechnologies reaches primary study endpoint in pivotal glioblastoma study: www.magforce.de/english/press/press-releases/pm/article-1257408385
Potential New Nanotherapy for Spinal Cord Injury
Polymeric micelles, which have long been under investigation as potential drug carriers, have been used directly as a medicine for spinal cord injuries by researchers from Purdue University (IN, USA). The treatment was found to be quicker than injections of polyethylene glycol, a traditional spinal cord injury therapy.
The team, led by Richard Borgens from the Center for Paralysis Research, injected monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) diblock copolymer micelles into injured spinal cord tissue in rats. They found that the treatment repaired and reduced calcuim influx in fibers within the spinal cord, named axons, which transmit electrical signals, confirmed by measurement of the axon‘s compound action potential.
The control group of rats that did not receive the micelle treatment had around 18% recovered axons at the end of the study, whereas those receiving the treatment had 60% repaired axons and had regained control of all of their limbs, also recovering locomotor function and showing much reduced inflammation.
“That was a very surprising discovery,” said Ji-Xin Cheng, coauthor of the study. “Micelles have been used for 30 years as drug-delivery vehicles in research, but no one has ever used them directly as a medicine.”
The team plan to perform further experiments to elucidate the mechanism by which the micelles repair axons, in order to further their potential as a spinal cord injury therapeutic.
Sources: Shi Y, Kim S, Huff TB et al.: Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles. Nat. Nanotech. (2009) (Epub ahead of print); Purdue University press release. Findings show nanomedicine promising for treating spinal cord injuries: http://news.uns.purdue.edu/x/2009b/091108ChengSpinal.html
Nanopillar Addition to Silicon Chip Assay Increases Sensitivity of Detection
A new method relying on nanotechnology to measure tumor metastasis by detecting the amount of circulating tumor cells in a patient‘s blood has been announced by researchers at the University of California, Los Angeles (CA, USA). The method is potentially faster, cheaper and more sensitive than currently existing methods and could represent an alternative to invasive biopsies. The technique has the potential to diagnose cancer, provide doctors with information on patient prognosis and also to monitor the effectiveness of treatments.
The detection technique is based on an existing method, in which a 1 × 2 cm silicon chip containing the sample to be tested is stained with immunofluorescence and the circulating tumor cells in the sample counted using an automated microscope. Senior author of the study, Professor Hsian-Rong Tseng, and his team adapted this method by adding densely packed nanopillars to the silicon chip, altering the topography of the chip and making the diagnosis more sensitive. The team believe that having a varied chip topography allows the chip to interact with nanosized components in blood cells, thus increasing the chip‘s sensitivity.
The chip was tested against a control chip with a flat surface, using an antiepithelial cell adhesion molecule that is specific to, and therefore able to detect and capture, tumor molecules.
The nanopillar-encrusted chip captured approximately 45–65% of the circulating tumor cells in a demonstration experiment using a culture medium containing breast cancer cells, compared with the 4–14% of cells found using the chip alone, a greater than tenfold improved sensitivity. The addition of the nanopillar surface also allowed researchers to reduce the time taken to complete the test from 3–4 h to only 2 h. Lead author of the study, Shutao Wang, said of the results: “The nanopillar chip captured more than 10-times the amount of cells captured by the currently used flat structure.”
Currently, the most popular method to diagnose tumor metastasis is a tumor biopsy, although this requires invasive surgery and potential sites for biopsy are difficult to locate in early stages of cancer. The new test method, using innovative lab-on-a-chip techniques, has been dubbed a ‘liquid biopsy’ by the team.
“We hope that this platform can provide a convenient and cost-efficient alternative to circulating tumor cell sorting by using mostly standard laboratory equipment,” commented Tseng, who is also part of the California NanoSystems Institute.
Further clinical research and other studies to ascertain the chip‘s efficacy at detecting circulating cancer cells in human serum, urine and abdominal fluids are planned by the team.
Sources: Wang S, Wang H, Jiao J et al.: Three-dimensional nanostructured substrates toward efficient capture of circulating tumor cells. Angew. Chem. Int. Ed. 48(47) 8970–8973 (2009); UCLA researchers create ‘fly paper’ to capture circulating cancer cells. University of California, Los Angeles press release: http://newsroom.ucla.edu/portal/ucla/ucla-researchers-create-fly-paper-112652.aspx