The efficacy of drug delivery and other nanomedicine-related therapies largely relies on the ability of nanoparticles to reach the target organ. However, when nanoparticles are injected into the bloodstream, their surface is instantly modified upon interaction with blood components, principally with proteins. It is well known that a dynamic and multi-layered protein structure is formed spontaneously on the nanoparticle upon contact with physiological media, which has been termed protein corona. Although several determinant factors involved in protein corona formation have been identified from in vitro studies, specific relationships between the nanomaterial synthetic identity and its ensuing biological identity under realistic in vivo conditions remain elusive. We present here a detailed study of in vivo protein corona formation after blood circulation of anisotropic gold nanoparticles (nanorods and nanostars). Plasmonic gold nanoparticles of different shapes and sizes were coated with polyethyleneglycol, intravenously administered in CD-1 mice and subsequently recovered. The results from gel electrophoresis and mass spectrometry analysis revealed the formation of complex protein coronas, as early as 10 minutes post-injection. The total amount of protein adsorbed onto the particle surface and the protein corona composition were found to be affected by both the particle size and shape.

Upon contact with a biological milieu, nanomaterials tend to interact with biomolecules present in the media, especially proteins, leading to the formation of the so-called “protein corona”. As a result of these nanomaterial–protein interactions, the bio-identity of the nanomaterial is altered, which is translated into modifications of its behavior, fate, and pharmacological profile. For biomedical applications, it is fundamental to understand the biological behavior of nanomaterials prior to any clinical translation. For these reasons, during the last decade, numerous publications have been focused on the investigation of the protein corona of many different types of nanomaterials. Interestingly, it has been demonstrated that the structure of the protein corona can be divided into hard and soft corona, depending on the affinity of the proteins for the nanoparticle surface. In the present document, we explore the differences between these two protein coronas, review the analysis techniques used for their assessment, and reflect on their relevance for medical purposes.

The present study is focused in finding an adequate therapeutic solution for the treatment of bone infection based on 3D multifunctional scaffolds, which combines the merits of osseous regeneration and local multidrug delivery. These 3D multidrug scaffolds, containing rifampin, levofloxacin and vancomycin, localized in different compartments to achieve different release kinetics. These 3D multidrug scaffolds displays an early and fast release of rifampin followed by sustained and prolonged release of vancomycin and levofloxacin, which are able to destroy Staphylococcus and Escherichia biofilms as well as inhibit bacteria growth in very short time periods. This new combined therapy approach involving the sequential delivery of antibiofilms with antibiotics constitutes an excellent and promising alternative for bone infection treatment.