Abstract
Protein corona of nanoparticles (NPs), which forms when these particles come in to contact with protein-containing fluids, is considered as an overlooked factor in nanomedicine. Through numerous studies it has been becoming increasingly evident that it importantly dictates the interaction of NPs with their surroundings. Several factors that determine the compositions of NPs protein corona have been identified in recent years, but one has remained largely ignored—the composition of media used for dispersion of NPs. Here, we determined the effect of dispersion media on the composition of protein corona of polyacrylic acid-coated cobalt ferrite NPs (PAA NPs) and silica NPs. Our results confirmed some of the basic premises such as NPs type-dependent specificity of the protein corona. But more importantly, we demonstrated the effect of the dispersion media on the protein corona composition. The differences between constituents of the media used for dispersion of NPs, such as divalent ions and macromolecules were responsible for the differences in protein corona composition formed in the presence of fetal bovine serum (FBS). Our results suggest that the protein corona composition is a complex function of the constituents present in the media used for dispersion of NPs. Regardless of the dispersion media and FBS concentration, majority of proteins from either PAA NPs or silica NPs coronas were involved in the process of transport and hemostasis. Interestingly, corona of silica NPs contained three complement system related proteins: complement factor H, complement C3 and complement C4 while PAA NPs bound only one immune system related protein, α-2-glycoprotein. Importantly, relative abundance of complement C3 protein in corona of silica NPs was increased when NPs were dispersed in NaCl, which further implies the relevance of dispersion media used to prepare NPs.
Highlights
Despite numerous advances of nanotechnology in the area of biomedicine in recent years, the technology itself did not completely fulfil high expectations in the field of medical applications [1]
Our results demonstrated that the medium in which NPs were dispersed had significantly affected NPs protein corona composition and could have an important implication on potential biological effects of NPs there was a clear difference in protein corona composition between dispersion of polyacrylic acidcoated cobalt ferrite NPs (PAA NPs) and silica NPs in complex media where macromolecular corona was formed (e.g. RPMI-1640 cell culture media (RPMI)) compared to media without macromolecules
By physico-chemical and proteomic characterization we demonstrated that the type of the dispersion media used to prepare NPs was relevant for protein corona composition
Summary
Despite numerous advances of nanotechnology in the area of biomedicine in recent years, the technology itself did not completely fulfil high expectations in the field of medical applications [1]. Problems with reproducibility and scaling up are sometimes tightly connected with insufficient characterization of nanomedicine formulations. To understand the effects of nanomedicines in vitro or in vivo, we need to consider several physicochemical parameters, such as size, size distribution, surface area, charge and surface chemistry which forms synthetic identity [4]. The second level of characterization is performed when nanomedicines interact with biological systems [5]. This biological identity is defined by adsorption of biomolecules, mainly proteins, to the surface of nanoparticles (NPs) and it is generally referred to as their protein corona [6,7,8,9,10]. Interaction between NPs and biological environment such as tissue and cells is mediated by this outmost layer of NPs, one of the frequently overlooked factor in the nanomedicine [11]
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