In vivo integrity of polymer-coated gold nanoparticles

Inorganic nanoparticles (NPs) are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well-known that their colloidal properties1 may change upon internalization by cells2, 3. While the stability of such NPs is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold NPs may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles (198Au)4 and engineered an 111In-labelled polymer shell around them5. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for 198Au and 111In showed partial removal of the polymer shell in vivo. While 198Au accumulates mostly in the liver, part of the 111In shows a non-particulate biodistribution similar to intravenous injection of chelated 111In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even NPs with high colloidal stability can change their physicochemical properties in vivo.