Nanotechnology, the science of the extremely tiny (one nanometer is one-billionth of a meter), is an important emerging industry with a projected annual market of around one trillion US dollars by 2015. It involves the control of atoms and molecules to create new materials with a variety of useful functions, including many that could be exceptionally beneficial in medicine. However, concerns are growing that it may have toxic effects, particularly damage to the lungs. Although nanoparticles have been linked to lung damage, it has not been clear how they cause it.
In a study published online June 11 in the newly launched Journal of Molecular Cell Biology Chinese researchers discovered that a class of nanoparticles being widely developed in medicine - ployamidoamine dendrimers (PAMAMs) – cause lung damage by triggering a type of programmed cell death known as autophagic cell death. They also showed that using an autophagy inhibitor prevented the cell death and counteracted nanoparticle-induced lung damage in mice.
Nanomaterials are now used in a variety of products, including sporting goods, cosmetics and electronics. The fact that unusual physical, chemical, and biological properties can emerge in materials at the nanoscale makes them particularly appealing for medicine. Scientists hope nanoparticles will be able to improve the effectiveness of drugs and gene therapy by carrying them to the right place in the body and by targeting specific tissues, regulating the release of drugs and reducing damage to healthy tissues. They also envision the possibility of implantable nano devices that would detect disease, treat it and report to the doctor automatically from inside the body. The US Food and Drug Administration has approved some first generation nanodrugs. One example is Abraxane, a nanoformulation of the anti-cancer chemotherapy paclitaxel.
Lung damage is the chief human toxicity concern surrounding nanotechnology, with studies showing that most nanoparticles migrate to the lungs. However, there are also worries over the potential for damage to other organs.
In the study, the researchers first showed, through several independent experiments, that several types of PAMAMs killed human lung cells in the lab. They did not observe any evidence that the cells were dying by apoptosis, a common type of programmed cell death. However, they found that the particles triggered autophagic cell death through the Akt-TSC2-mTOR signalling pathway. Autophagy is a process that degrades damaged materials in a cell and plays a normal part in cell growth and renewal, but scientists have found that sometimes an overactivity of this destruction process leads to cell death.
The researchers also found that treating the cells with an autophagy inhibitor known as 3MA significantly inhibited the process, increasing the number of cells that survived exposure to the nanoparticles.
"Those results, taken together, showed that autophagy plays a critical role in the nanoparticle-induced cell death," said Dr. Jiang.
The scientists then tested their findings in mice. They found that introducing the toxic nanoparticles significantly increased lung inflammation and death rates in the mice, but injecting the mice with the autophagy inhibitor 3MA before introducing the nanoparticles significantly ameliorated the lung damage and improved survival rates.
It is not clear whether other types of nanoparticles would cause lung damage via the same mechanism, but some may, Dr. Jiang said.
Steve - this is why we have abstained from recommending foods or dietary supplements that incorporate nanotechnology. There are too many unknowns at this time. We know the science has an incredible future, but as with most rapidly advancing science, the safety studies come after the fact.