Nanoparticle size is a critical physicochemical determinant of the human blood plasma corona: a comprehensive quantitative proteomic analysis.

In biological fluids, proteins associate with nanoparticles, leading to a protein "corona" defining the biological identity of the particle. However, a comprehensive knowledge of particle-guided protein fingerprints and their dependence on nanomaterial properties is incomplete. We studied the long-lived ("hard") blood plasma derived corona on monodispersed amorphous silica nanoparticles differing in size (20, 30, and 100 nm). Employing label-free liquid chromatography mass spectrometry, one- and two-dimensional gel electrophoresis, and immunoblotting the composition of the protein corona was analyzed not only qualitatively but also quantitatively. Detected proteins were bioinformatically classified according to their physicochemical and biological properties. Binding of the 125 identified proteins did not simply reflect their relative abundance in the plasma but revealed an enrichment of specific lipoproteins as well as proteins involved in coagulation and the complement pathway. In contrast, immunoglobulins and acute phase response proteins displayed a lower affinity for the particles. Protein decoration of the negatively charged particles did not correlate with protein size or charge, demonstrating that electrostatic effects alone are not the major driving force regulating the nanoparticle-protein interaction. Remarkably, even differences in particle size of only 10 nm significantly determined the nanoparticle corona, although no clear correlation with particle surface volume, protein size, or charge was evident. Particle size quantitatively influenced the particle's decoration with 37% of all identified proteins, including (patho)biologically relevant candidates. We demonstrate the complexity of the plasma corona and its still unresolved physicochemical regulation, which need to be considered in nanobioscience in the future.

Assessment of tumor development and wound healing using endoscopic techniques in mice.

Mouse models of intestinal inflammation and colon cancer are valuable tools to gain insights into the pathogenesis of the corresponding human diseases. Recently, in vivo mouse endoscopy has been developed, allowing not only the high-resolution monitoring and scoring of experimental disease development, but also enables the investigator to perform manipulations, including local injection of reagents or the taking of biopsies for molecular and histopathologic analyses. Chromoendoscopic staining with methylene blue enables visualization of the crypt structure and allows discrimination between inflammatory and neoplastic changes. The development of endoscopic techniques in live mice opened new options for the investigation of disease mechanisms in the gut and for the preclinical testing of potential therapeutic effects of drug candidates. Finally, mouse endoscopy can help to reduce animal numbers needed to gain significant experimental data.