The In Vivo Biological Fate of Protein Corona: A Comparative PET Study of the Fate of Soft and Hard Protein Corona in Healthy Animal Models.

Radiolabeling and nuclear imaging techniques are used to investigate the biodistribution patterns of the soft and hard protein corona around poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) after administration to healthy mice. Soft and hard protein coronas of 131I-labeled BSA or 131I-labeled serum are formed on PLGA NPs functionalized with either polyehtylenimine (PEI) or bovine serum albumin (BSA). The exchangeability of hard and soft corona is assessed in vitro by gamma counting exposing PLGA NPs with corona to non-labeled BSA, serum, or simulated body fluid. PEI PLGA NPs form larger and more stable coronas than BSA PLGA NPs. Soft coronas are more exchangeable than hard ones. The in vivo fate of PEI PLGA NPs coated with preformed 18F-labeled BSA hard and soft coronas is assessed by positron emission tomography (PET) following intravenous administration. While the soft corona shows a biodistribution similar to free 18F BSA with high activity in blood and kidney, the hard corona follows patterns characteristic of nanoparticles, accumulating in the lungs, liver, and spleen. These results show that in vivo fates of soft and hard corona are different, and that soft corona is more easily exchanged with proteins from the body, while hard corona is largely retained on the nanoparticle surface.

Inside the Protein Corona: From Binding Parameters to Unstained Hard and Soft Coronas Visualization.

Proteins spontaneously adsorb on nanoparticle surfaces when injected into the bloodstream. It drastically modifies the nanoparticle's fate and how they interact with organs and cells. Although this protein layer (protein corona) has been widely studied, the robustness of the most employed characterization methods and the visualization of its unstained fractions remain open questions. Here, synchrotron-based small-angle X-ray scattering was used to follow the corona formation and estimate binding parameters. At the same time, transmission electron microscopy under cryogenic conditions associated with cross-correlation image processing and energy-filtered transmission electron microscopy allowed to determine protein corona morphology and thickness together with the visualization of its unstained hard and soft fractions. The above-presented strategy shows tremendous potential for deciphering fundamental protein corona aspects and can contribute to rational medical nanoparticle engineering.

Hard and Soft Protein Corona of Nanomaterials: Analysis and Relevance.

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.

Recent advances in the analysis of nanoparticle-protein coronas.

In spite of radical advances in nanobiotechnology, the clinical translation of nanoparticle (NP)-based agents is still a major challenge due to various physiological factors that influence their interactions with biological systems. Recent decade witnessed meticulous investigation on protein corona (PC) that is the first surrounds NPs once administered into the body. Formation of PC around NP surface exhibits resilient effects on their circulation, distribution, therapeutic activity, toxicity and other factors. Although enormous literature is available on the role of PC in altering pharmacokinetics and pharmacodynamics of NPs, understanding on its analytical characterization methods still remains shallow. Therefore, the current review summarizes the impact of PC on biological fate of NPs and stressing on analytical methods employed for studying the NP-PC.

How protein coronas determine the fate of engineered nanoparticles in biological environment.

Nanomedicine is a booming medical field that utilises nanoparticles (NPs) for the development of medicines, medical devices, and diagnostic tools. The behaviour of NPs in vivo may be quite complex due to their interactions with biological molecules. These interactions in biological fluids result in NPs being enveloped by dynamic protein coronas, which serve as an interface between NPs and their environment (blood, cell, tissue). How will the corona interact with this environment will depend on the biological, chemical, and physical properties of NPs, the properties of the proteins that make the corona, as well as the biological environment. This review summarises the main characteristics of protein corona and describes its dynamic nature. It also presents the most common analytical methods to study the corona, including examples of protein corona composition for the most common NPs used in biomedicine. This knowledge is necessary to design NPs that will create a corona with a desired efficiency and safety in clinical use.

The effect of the protein corona on the interaction between nanoparticles and lipid bilayers.

HYPOTHESIS: It is known that nanoparticles (NPs) in a biological fluid are immediately coated by a protein corona (PC), composed of a hard (strongly bounded) and a soft (loosely associated) layers, which represents the real nano-interface interacting with the cellular membrane in vivo. In this regard, supported lipid bilayers (SLB) have extensively been used as relevant model systems for elucidating the interaction between biomembranes and NPs. Herein we show how the presence of a PC on the NP surface changes the interaction between NPs and lipid bilayers with particular care on the effects induced by the NPs on the bilayer structure. EXPERIMENTS: In the present work we combined Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) and Neutron Reflectometry (NR) experimental techniques to elucidate how the NP-membrane interaction is modulated by the presence of proteins in the environment and their effect on the lipid bilayer. FINDINGS: Our study showed that the NP-membrane interaction is significantly affected by the presence of proteins and in particular we observed an important role of the soft corona in this phenomenon.