Mussel-Inspired Polydopamine: A Biocompatible and Ultrastable Coating for Nanoparticles <i>in Vivo</i>

Bioinspired polydopamine (PDA) has served as a universal coating to nanoparticles (NPs) for various biomedical applications. However, one remaining critical question is whether the PDA shell on NPs is stable <i>in vivo</i>. In this study, we modified gold nanoparticles (GNPs) with finely controlled PDA nanolayers to form uniform core/shell nanostructures (GNP@PDA). <i>In vitro</i> study showed that the PDA-coated GNPs had low cytotoxicity and could smoothly translocate to cancer cells. Transmission electron microscopy (TEM) analysis demonstrated that the PDA nanoshells were intact within cells after 24 h incubation. Notably, we found the GNP@PDA could partially escape from the endosomes/lysosomes to cytosol and locate close to the nucleus. Furthermore, we observed that the PDA-coated NPs have very different uptake behavior in two important organs of the liver and spleen: GNP@PDA in the liver were mainly uptaken by the Kupffer cells, while the GNP@PDA in the spleen were uptaken by a variety of cells. Importantly, we proved the PDA nanoshells were stable within cells of the liver and spleen for at least six weeks, and GNP@PDA did not show notable histological toxicity to main organs of mice in a long time. These results provided the direct evidence to support that the PDA surface modification can serve as an effective strategy to form ultrastable coatings on NPs <i>in vivo</i>, which can improve the intracellular delivery capacity and biocompatibility of NPs for biomedical application