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Correlating Corona Composition and Cell Uptake to Identify Proteins Affecting Nanoparticle Entry into Endothelial Cells.

ABSTRACT: The formation of the biomolecule corona on the surface of nanoparticles upon exposure to biological fluids critically influences nanocarrier performance in drug delivery. It has been shown that in some cases corona proteins can mediate specific nanoparticle interactions with cell receptors. Within this context, in order to identify corona proteins affecting nanoparticle uptake, in this work, correlation analysis is performed between the corona composition of a panel of silica nanoparticles of different sizes and surface functionalities and their uptake in four endothelial cell types derived from different organs. In this way, proteins that correlate with increased or decreased uptake were identified, and their effects were validated by studying the uptake of nanoparticles coated with a single protein corona and competition studies in brain and liver endothelium. The results showed that precoating nanoparticles with histidine-rich glycoprotein (HRG) alone strongly decreased uptake in both liver and brain endothelium. Furthermore, our results suggested the involvement of the transferrin receptor in nanoparticle uptake in liver endothelium and redirection of the nanoparticles to other receptors with higher uptake efficiency when the transferrin receptor was blocked by free transferrin. These data suggested that changes in the cell microenvironment can also affect nanoparticle uptake and may lead to a different interaction site with nanoparticles, affecting their uptake efficiency. Overall, correlating the composition of the protein corona and nanoparticle uptake by cells allows for the identification of corona molecules that can be used to increase as well as to reduce nanoparticle uptake by cells.

SUBMITTER: Aliyandi A

PROVIDER: S-EPMC8672348 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The potential applications of nanomaterials as drug delivery systems and in other products continue to expand. Upon introduction into physiological environments and driven by energetics, nanomaterials readily associate proteins forming a protein corona (PC) on their surface. This PC influences the nanomaterial's surface characteristics and may impact their interaction with cells. To determine the biological impact of nanomaterial exposure as well as nanotherapeutic applications, it is necessary to understand PC formation. Utilizing a label-free mass spectrometry-based proteomics approach, we examined the composition of the PC for a set of four silver nanoparticles (AgNPs) including citrate-stabilized and polyvinlypyrrolidone-stabilized (PVP) colloidal silver (20 or 110 nm diameter). To simulate cell culture conditions, AgNPs were incubated for 1 h in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum, washed, coronal proteins solubilized, and proteins identified and quantified by label-free LC-MS/MS. To determine which attributes influence PC formation, the AgNPs were characterized in both water and cell culture media with 10% FBS. All AgNPs associated a common subset of 11 proteins including albumin, apolipoproteins, keratins, and other serum proteins. 110 nm citrate- and PVP-stabilized AgNPs were found to bind the greatest number of proteins (79 and 85 respectively) compared to 20 nm citrate- and PVP-stabilized AgNPs (45 and 48 respectively), suggesting a difference in PC formation based on surface curvature. While no relationships were found for other protein parameters (isoelectric point or aliphatic index), the PC on 20 nm AgNPs (PVP and citrate) consisted of more hydrophobic proteins compared to 110 nm AgNPs implying that this class of proteins are more receptive to curvature-induced folding and crowding in exchange for an increased hydration in the aqueous environment. These observations demonstrate the significance of electrostatic and hydrophobic interactions in the formation of the PC which may have broad biological and toxicological implications.

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Correlating Corona Composition and Cell Uptake to Identify Proteins Affecting Nanoparticle Entry into Endothelial Cells.

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