To the Editor

Yamashita et al. (Nature Nanotech. 6, 321–328; 2011) report that silica and titanium dioxide (TiO2) nanoparticles with diameters of 70 nm and 35 nm, respectively, can cross the placental barrier in pregnant mice. Using transmission electron microscopy (TEM), the researchers claim that nanoparticles are found in the liver and brain of the fetus. Although TEM is useful for the qualitative examination of nanoparticles, it is not sensitive enough for studying the trans-placental transport of TiO2 nanoparticles.

Assuming that the concentration of TiO2 nanoparticles in the fetal liver is one nanogram per gram of liver (the density of liver is approximately 1.1 g cm−3) and that the mass of a 35 nm TiO2 particle is approximately 1 × 10−16 g (the density of rutile-TiO2 is 4.3 g cm−3), on average, only one nanoparticle can theoretically be found in a 1 mm2 section of liver tissue (an ultrathin section usually has a thickness of less than 100 nm). The TEM images collected by Yamashita et al. showed a dark electron-dense spot in a field size of 5 μm × 5 μm. Based on our estimation, on average, tens of thousands of such images need to be examined to find one TiO2 nanoparticle. This means that the TEM results cannot firmly prove that nanoparticles were present in the fetal liver and brain, unless the concentration of nanoparticles in the fetal liver is several orders of magnitude higher than the hypothetical value of one nanogram per gram.

In conclusion, more suitable quantitative methods should be used to study the biodistribution of nanoparticles in pregnant mice.