Time-evolution of in vivo protein corona onto blood-circulating PEGylated liposomal doxorubicin (DOXIL) nanoparticles

TLDR

Nanoparticles rapidly acquire a protein corona upon entering blood, and the composition of this corona is thought to depend on exposure time, yet its in vivo dynamics remain largely unknown. This study aimed to quantitatively and qualitatively track the time evolution of the protein corona on clinically used PEGylated liposomal doxorubicin. Protein adsorption profiles were measured at 10 min, 1 h, and 3 h after intravenous injection of liposomes into CD‑1 mice. A complex corona appeared within 10 min, and although total protein levels stayed constant, fluctuating protein abundances revealed highly dynamic binding kinetics.

Abstract

Nanoparticles (NPs) are instantly modified once injected in the bloodstream because of their interaction with the blood components. The spontaneous coating of NPs by proteins, once in contact with biological fluids, has been termed the 'protein corona' and it is considered to be a determinant factor for the pharmacological, toxicological and therapeutic profile of NPs. Protein exposure time is thought to greatly influence the composition of protein corona, however the dynamics of protein interactions under realistic, in vivo conditions remain unexplored. The aim of this study was to quantitatively and qualitatively investigate the time evolution of in vivo protein corona, formed onto blood circulating, clinically used, PEGylated liposomal doxorubicin. Protein adsorption profiles were determined 10 min, 1 h and 3 h post-injection of liposomes into CD-1 mice. The results demonstrated that a complex protein corona was formed as early as 10 min post-injection. Even though the total amount of protein adsorbed did not significantly change over time, the fluctuation of protein abundances observed indicated highly dynamic protein binding kinetics.