The adsorption of serum proteins on biomaterial surfaces is a critical determinant for the outcome of medical procedures and therapies, which involve inserting materials and devices into the body. In Show more
The adsorption of serum proteins on biomaterial surfaces is a critical determinant for the outcome of medical procedures and therapies, which involve inserting materials and devices into the body. In this study, we aimed to understand how surface topography at the nanoscale influences the composition of the protein corona that forms on the (bio)material surface when placed in contact with serum proteins. To achieve that, we developed nanoengineered model surfaces with finely tuned topography of 16, 40, and 70 nm, overcoated with methyl oxazoline to ensure uniform outermost chemistry across all surfaces. Our findings revealed that within the studied height range, surface nanotopography had no major influence on the overall quantity of adsorbed proteins. However, significant alterations were observed in the composition of the adsorbed protein corona. For instance, clusterin adsorption decreased on all the nanotopography-modified surfaces. Conversely, there was a notable increase in the adsorption of ApoB and IgG gamma on the 70 nm nanotopography. In comparison, the adsorption of albumin was greater on surfaces that had a topography scale of 40 nm. Analysis of the gene enrichment data revealed a reduction in protein adsorption across all immune response-related biological pathways on nanotopography-modified surfaces. This reduction became more pronounced for larger surface nanoprotrusions. Macrophages were used as representative immune cells to assess the influence of the protein corona composition on inflammatory outcomes. Gene expression analysis demonstrated reduced inflammatory responses on the nanotopographically modified surface, a trend further corroborated by cytokine analysis. These findings underscore the potential of precisely engineered nanotopography-coated surfaces for augmenting biomaterial functionality. Show less
Immunosuppression with glucocorticoids is a common treatment for autoimmune liver diseases and after liver transplant, which is however associated with severe side-effects. Targeted delivery of glucoc Show more
Immunosuppression with glucocorticoids is a common treatment for autoimmune liver diseases and after liver transplant, which is however associated with severe side-effects. Targeted delivery of glucocorticoids to inflammatory cells, e.g. liver macrophages and Kupffer cells, is a promising approach for minimizing side effects. Herein, we prepare core-shell silica nanocapsules (SiO Show less
Understanding nanoparticle-protein interactions is a crucial issue in the development of targeted nanomaterial delivery. Besides unraveling the composition of the nanoparticle's protein coronas, disti Show more
Understanding nanoparticle-protein interactions is a crucial issue in the development of targeted nanomaterial delivery. Besides unraveling the composition of the nanoparticle's protein coronas, distinct proteins thereof could control nanoparticle uptake into specific cell types. Here we differentially analyzed the protein corona composition on four polymeric differently functionalized nanoparticles by label-free quantitative mass spectrometry. Next, we correlated the relative abundance of identified proteins in the corona with enhanced or decreased cellular uptake of nanoparticles into human cancer and bone marrow stem cells to identify key candidates. Finally, we verified these candidate proteins by artificially decorating nanoparticles with individual proteins showing that nanoparticles precoated with the apolipoproteins ApoA4 or ApoC3 significantly decreased the cellular uptake, whereas precoating with ApoH increased the cellular uptake. Show less