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Nanomaterials in common products cause cell "leakiness"

27 May 2013

Dr Leong (centre), PhD Student Ms Magdiel Inggrid Setyawati (left) and Postdoctoral Fellow Dr Dalton Tay with a background screen showing NanoEL

Titanium dioxide nanoparticles showing leakiness at the cellular and lung vasculature level. Spaces formed between endothelial cells are indicated with red arrow heads. Leakiness in lung vasculature can lead to increased metastasis of cancer cells.

With nanomaterials being consumed in many everyday products such as food and cosmetics, there is growing safety concerns about the tiny particles interacting with living tissues. Animal studies show that nanoparticles accumulating in internal organs are likely to have passed through protective cell barriers to reach the affected organs, in a process known as endocytosis.

This conventional theory has now been challenged with the discovery by a group of researchers led by Dr David Leong from the NUS Department of Chemical and Biomolecular Engineering. Together with collaborators from Singapore's Agency for Science, Technology and Research and Nanyang Technological University, the alternative mechanism uncovered could help provide understanding to better and safer design of biological nanomaterials.

The paper "Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin" published recently in Nature Communications found that nanomaterials could cause gaps to form between endothelial cells lining the inside of blood and lymphatic vessels within minutes after exposure to the particles. Naming it "nanomaterials induced endothelial cells leakiness" (NanoEL), this process happens more rapidly and easily than the endocytosis path.

The newly discovered effect is caused by the physical interaction between titanium dioxide nanomaterials and an endothelial cell protein that holds the cells together. Experiments showed that injections of the nanomaterials cause leakiness of blood vessels under the skin in mice; in a mouse model with skin cancer, the cancer cells leak out of blood vessels and spread to vital organs such as lungs. However, the authors qualified that the high doses of nanomaterials used in the studies are for proof-of-concept purposes.

NanoEL is not limited to a specific type of material; besides titanium dioxide (23.5 nm in size), the investigators have observed the process in silicon dioxide (15 nm) and silver (20 nm) nanomaterials - compounds commonly present in edible products, cosmetics and toiletries. For perspective, 10 nm is about 1/5,000 the diameter of a strand of human hair.

Dr Leong said that the team is currently studying the characteristics of the nanoparticles that trigger the effect to explore opportunities presented by the induced phenomenon for drug treatment, such as delivering therapeutic agents to hard-to-reach regions in the body.