Simple in vitro assays that evaluate the stability of polymer-coated nanoparticles may not accurately predict the nanoparticles’ fate after injection into mammals, according to a study (Nat. Nanotechnol. 2015, DOI: 10.1038/nnano.2015.111). Metal nanoparticles, which are being evaluated for numerous pharmaceutical applications, are typically wrapped in a polymer shell to stabilize the particles and prevent agglomeration. But what happens to the core-shell structures in vivo is not well-known. To answer that question, a team led by Wolfgang G. Kreyling of the German Research Center for Environmental Health, in Munich, and Wolfgang J. Parak of Philipps University, in Marburg, Germany, prepared radiolabeled gold (198Au) nanoparticle cores, coated them with a polymer containing a different radiolabel (111In), and injected the coated particles into rats. Analyses of tissues and organs show that the shells are partially removed in vivo. The nanoparticle cores tend to accumulate in the liver, and fragments of the polymer shells are excreted through the kidneys. In vitro analyses with liver and umbilical cells show that largely intact nanoparticles are localized in endosomal and lysosomal compartments. In vitro control tests show that proteolytic enzymes can decompose the core-shell particles. The team proposes that similar digestion processes occur in vivo.