Nanoparticles (NPs) are instantly modified once injected in the bloodstream because of their interaction with the blood components. The spontaneous self-assembly of proteins onto NP surfaces once in contact with biological fluids, has been termed the ‘protein corona’ and it is considered to be a determinant factor of the pharmacological, toxicological and therapeutic profiles of nanoscale medicines. The dynamic process of protein adsorption onto the NP surface has been evaluated extensively by the incubation of NPs with in various plasma-containing media. However, the extrapolation of such in vitro studies to predict the fate of NPs in vivo remains mainly speculative and largely untested. Our aim was to study in vivo the dynamic protein corona formation onto three different types of clinically tested liposome systems (bare, PEGylated and antibody-conjugated). The formation of in vivo protein corona was determined after the recovery of tail-vein injected liposomes from the blood circulation of CD-1 mice, 10 min post-injection. In comparison, in vitro protein corona was formed by the incubation of liposomes in CD-1 mouse plasma. In vivo and in vitro formed protein coronas were compared in terms of morphology, composition and cellular internalisation. Overall, even though the total amount of protein adsorbed onto circulating liposomes in vivo was comparable with that observed from in vitro incubations, the protein species that self-assembled onto the liposomes in vivo were considerably more, leading to a molecularly ‘richer’ protein corona. We then investigated how protein exposure time influenced the composition of the self-assembled protein corona, to elucidate the dynamics of protein interactions under in vivo conditions. Results of a time-resolved, in vivo protein corona study of PEGylated liposomal doxorubicin, identical to the clinical product Doxil® will be shown.

In vivo biomolecule corona onto clinically-used blood-circulating liposomes

253rd National Meeting (2017)

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