Self-assembled protein capsids have gained attention as a promising class of nanoparticles for biomedical applications due to their monodisperse nature and versatile genetic and chemical taUorability. To determine the plasma clearance and tissue distribution in mice of the versatile capsid of bacteriophage Qβ, the particles were decorated with gadolinium complexes using the Cu'-mediated azide-alkyne cycloaddition reaction. Interior surface labeling was engineered by the introduction of an azide-containing unnatural amino acid into the coat protein for the first time. Clearance rates were conveniently monitored by quantitative detection of Gd using inductively coupled plasma optical emission spectroscopy and were found to be inversely proportional to the number of complexes attached to the exterior surface of the particle. This phenomenon was correlated to changes in exterior surface charge brought about by acylation of surface-exposed amine groups in the initial step of the bioconjugation protocol. When primary amine groups were reintroduced by azide-alkyne coupling, the circulation time increased accordingly. These results show that nanoparticle trafficking may be tailored in predictable ways by chemical and genetic modifications that modulate surface charge.
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