Biotechnology: remote control of living cells.

nature nanotechnology | VOL 3 | JANUARY 2008 | www.nature.com/naturenanotechnology 13 that accumulation in each of the organs is determined by size. Although the results show that size matters in biodistribution, it is still unclear why it can markedly affect the way the particles are distributed in vivo. Finally, none of the nanoparticles used in the study appeared to readily cross the blood–brain barrier. Another important finding of the study was the apparent retention of nanoparticles in the animals over the period of the experiment. Total urinary and faecal excretion after four days was greatest for the 5-nm positively charged nanoparticles, but less than 50% of the total dose was accounted for. Total excretion was much lower (between 6–15% of the total dose) for all the other nanoparticles, and the persistence of material in the tissues confirmed these observations. These data suggest that the particles entered the peripheral tissues and became either tightly bound or highly compartmentalized. This implies that with repeated exposure, accumulation will occur over time regardless of the size or surface properties of the nanoparticles. Such long-term exposure and accumulation may lead to local tissue damage and requires further investigation. Intuitively, one might expect that the size and surface properties of nanoparticles would be sufficient to define how they distribute in vivo. If this was the case, we could create a variety of nanoparticles by varying these two parameters and know exactly how they behave in vivo. However, this may be too simplistic a model. The internal composition of the nanoparticle may also influence how and where they are taken up. Indeed, the Roswell–Michigan team found that gold–dendrimer composites and nanoparticles made entirely of dendrimer behaved quite differently despite having the same size and surface charge. Michael Welch, Karen Wooley and colleagues5 at Washington University have reported a similar finding using PEGylated-shell crosslinked nanoparticles. It is possible that the core of the nanoparticle influences its interaction with biological systems by altering the dendrimer configuration. Studies that address the basic pharmacokinetics of such nanostructures are invaluable for understanding and predicting their distribution in vivo. Moreover, the present study suggests that size and charge, and probably the internal core of the nanoparticle, are important considerations when designing ‘targeted’ systems. Though promising, it is still necessary to investigate a larger range of nanoparticle sizes and to uncover the reasons for how the interior of a nanoparticle influences its pharmacokinetics.