In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

Abstract

Understanding the basic interactions between engineered nanoparticles (ENPs) and biological systems is essential for evaluating ENPs’ safety and developing better nanomedicine. Profound interactions between ENPs and biomolecules such as proteins are inevitable to occur when ENPs are administered or exposed to biological systems, for example, through intravenous injection, oral, or respiration. As a key component of these interactions, protein corona (PC) is immediately formed surrounding the outlayer of ENPs. PC formation is crucial because it gives ENPs a new biological identity by altering not only the physiochemical properties, but also the biobehaviors of ENPs. In the past two decades, most investigations about PC formation were carried out with in vitro systems which could not represent the true events occurring within in vivo systems. Most recently, studies of in vivo PC formation were reported, and it was found that the protein compositions and structures were very different from those formed in vitro. Herein, we provide an in-time review of the recent investigations of this in vivo PC formation of ENPs. In this review, commonly used characterization methods and compositions of in vivo PC are summarized firstly. Next, we highlight the impacts of the in vivo PC formation on absorption, blood circulation, biodistribution, metabolism, and toxicity of administered ENPs. We also introduce the applications of modulating in vivo PC formation in nanomedicine. We further discuss the challenges and future perspectives.

Theophylline-encapsulated Nile Tilapia fish scale-based collagen nanoparticles effectively target the lungs of male Sprague–Dawley rats

“…Transmission electron microscopy analysis showed an exterior protein shell that decorated the surface of most of the Nile Tilapia fish scale-based collagen nanoparticles, forming what is known as ‘protein’ or ‘bio corona.’ This finding agrees with Gunawan et al, and Bai et al, who highlighted that the presence of protein corona–cell interactions might have either beneficial or adverse biological effects on nanomedicine 32 , 33 . These effects include ease-of-targeted delivery, cell-specific uptake of therapeutic nanoparticles, vaccine development based on engineered nanoparticles as adjuvants, and reduction of the nanoparticles’ immunotoxicity 34 .…”

One-Step Synthesis of Nanoliposomal Copper Diethyldithiocarbamate and Its Assessment for Cancer Therapy

“…The presence of anionic PEG chains on the surface of nanoliposomes has been shown to recruit a distinct protein corona in plasma that may result in decreased complement activation and clearance by the reticuloendothelial system (RES) [ 38 ]. Additionally, decorating nanoliposomes with surface functional groups would facilitate the development of novel nanomaterial designs using crosslinking chemistry to potentially improve the formulation’s targetability [ 39 ]. The surface functionalization of the nanoliposomes with a carboxylic acid group recruits a protein corona that is different from the one seen with PEG 2000 -Me groups in mouse plasma ( Figure 6 ).…”

Safety Assessment of 2D MXenes: In Vitro and In Vivo

“…Many studies cited in this review did not provide full information regarding the physiochemical properties of the MXenes that were tested. In addition, while protein corona formation is known as a key factor affecting the interactions between MXenes and biological systems [ 60 , 61 , 62 ], no studies have considered this factor in toxicology studies. The influence of protein corona composition on MXenes and their behaviors in biological systems needs to be clarified so as to further the understanding of toxicological mechanisms.…”