Effect of initial particle size and surface charge on the formation of the plasma protein corona on chitosan‐based nanoparticles

Abstract When a nanoparticle interacts with the biological environment, its surface is covered by a layer of biomolecules such as proteins and lipids called a protein corona. Given the importance and impact of the protein corona on the fate of nanoparticles in the body, it is important to study the interaction of nanoparticles with proteins. This study investigated the impact of the initial size and surface charge of nanoparticles on the changes in protein corona thickness on chitosan‐based nanoparticles after exposure to blood plasma. To be able to separate the chitosan‐based nanoparticles from the blood plasma, magnetic nanoparticles were coated with chitosan (with a positive charge) and carboxymethyl chitosan (CMC; with a negative charge) in two different size ranges of 200–250 and 300–350 nm. The coated nanoparticles' chemical composition, properties, and morphology were investigated using Fourier‐transform infrared spectroscopy, X‐ray diffraction, dynamic light scattering (DLS), zeta potential measurements, transmission electron microscopy, and field emission scanning electron microscope. The results confirmed the formation of nanoparticles based on chitosan and CMC. Subsequently, these nanoparticles were exposed to blood plasma to examine the protein corona that formed. The DLS and zeta potential measurements showed that the surface charge and particle size of the nanoparticles significantly influenced the formation of the protein corona. The results revealed that the smaller particle size and the positive surface charge of the nanoparticles resulted in the formation of a thicker corona. In addition, it showed that after exposure to the blood plasma proteins, the positive charge of the particles changed to a negative charge.