Personalized protein corona on nanoparticles and its clinical implications

Abstract

It is now well understood that once in contact with biological fluids, nanoscale objects lose their original identity and acquire a new biological character, referred to as a protein corona. The protein corona changes many of the physicochemical properties of nanoparticles, including size, surface charge, and aggregation state. These changes, in turn, affect the biological fate of nanoparticles, including their pharmacokinetics, biodistribution, and therapeutic efficacy. It is progressively being accepted that even slight variations in the composition of a protein source (e.g., plasma and serum) can substantially change the composition of the corona formed on the surface of the exact same nanoparticles. Recently it has been shown that the protein corona is strongly affected by the patient's specific disease. Therefore, the same nanomaterial incubated with plasma proteins of patients with different pathologies adsorb protein coronas with different compositions, giving rise to the concept of personalized protein corona. Herein, we review this concept along with recent advances on the topic, with a particular focus on clinical relevance.

Figure 1. Disease-dependent personalized protein corona

The biological environment that comes into contact with NPs affects the protein corona (PC): plasma protein alterations due to disease conditions affect the type, amount, and conformation of proteins that compose the corona. Reproduced from Ref. [] with permission from Royal Society of Chemistry.

Figure 2. Personalized protein corona general concept

Gender, habits, age, diseases, temporary drug consumption, pregnancy, and geographical origin all potentially affect the protein plasma composition. This, in turn, affects the protein corona composition. As a consequence, this information has to be provided when working with human plasma, not only to better interpret the obtained results but also to give useful information for the design of the safe and efficient nanoparticles in a disease-specific manner. NP: nanoparticle, PPs: plasma proteins

Figure 3. Personalized protein corona in healthy volunteers

A) 1D-SDS PAGE image of the protein corona profiles formed around liposomes when incubated for 1h with human plasma from five healthy volunteers. B) Intensity of lanes analyzed by ImageJ showing that the protein coronas are different in abundance among the 5 healthy donors. C) Band intensity according to the molecular weights. D) The top 4 most abundant band intensities are compared among the 5 samples. Results are presented as average ± SD. Reproduced from Ref. [] with permission from Elsevier publishing group.

Figure 4. Disease-dependent protein conformational changes

A) When a protein conformational change occurs, the secondary or tertiary structure of a protein is modified and its biological function is affected. B) Various diseases arise from protein conformational changes. C) The same protein in the plasma of patients with different diseases can have a different conformation D) This affects the interaction of the protein with the surface of nanoparticles and consequently alters participation of other proteins in the corona composition. NP: nanoparticle; PP: plasma protein.

Figure 5. Disease-dependent apoptosis and necrosis

MCF-7 breast cancer cells were stained using propidium iodide (nuclei, green) and annexinV (membrane, yellow to red). The cells were then incubated for 24h with corona-coated GO from patients with different diseases (A-J). The results show that the protein coronas from different diseases have different impacts on apoptosis (green) and late apoptosis/necrosis (yellow/green-red) levels. GO: graphene oxide. Reproduced from Ref. [] with permission from Royal Society of Chemistry.