Abstract
BackgroundNanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. In addition to dimension, charge and material the distinct protein corona influences the interplay of nanoparticles with tissue barriers. In this study we were focused on the impact of in situ formed human plasma protein corona on the transfer of 80 nm polystyrene nanoparticles (PS-particles) across the human placenta. To study materno-to fetal PS transfer we used the human ex vivo placental perfusion approach, which represents an intact and physiological tissue barrier. To analyze the protein corona of PS particles we performed shotgun proteomics of isolated nanoparticles before and after tissue exposure.ResultsHuman plasma incubated with PS-particles of 80 nm and subsequent formed protein corona enhanced the transfer across the human placenta compared to PS-corona formed by bovine serum albumin and dextran which served as a control. Quantitative and qualitative changes of plasma proteins determined the changes in PS transfer across the barrier. Based on the analysis of the PS-proteome two candidate proteins, namely human albumin and immunoglobulin G were tested if these proteins may account for the enhanced PS-transfer across the placenta. Interestingly, the protein corona formed by human albumin significantly induced the transfer of PS-particles across the tissue compared to the formed IgG-corona.ConclusionIn total we demonstrate the PS corona dynamically and significantly evolves upon crossing the human placenta. Thus, the initial composition of PS particles in the maternal circulation is not predictive for their transfer characteristics and performance once beyond the barrier of the placenta. The precise mechanism of these effects remains to be elucidated but highlights the importance of using well designed biological models when testing nanoparticles for biomedical applications.
Highlights
Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona
The smallest massmedian-diameter (D50) particle sizes (96.4 ± 0.4 nm) were recorded in phosphate buffered saline (PBS), which served as a reference
Here we explored if and how plasma proteins may alter the transfer of unmodified PS-particles across the placental barrier
Summary
Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. The NP-protein biocorona highly defines distribution and retention of NPs in tissues, as well as their interstitial transport which determines NP toxicity [12,13,14]. For such nano-interface in vitro studies cell culture media supplemented either with albumin, serum or anti-coagulated human plasma are frequently used [15]. These studies demonstrated supplementation specific effects of adhering proteins on NP retention at cellular targets [16, 17]. The composition of the protein corona is species-specific, which is an inherent limitation of animal models when extrapolating data to humans [19]
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