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The magnitude of this effect is strongly dependent both on surface and structure of the nanoparticle. To define the contribution of the internal nanoparticle structure, protein corona formation of block copolymer micelles with poly(<jats:italic>N<\/jats:italic>\u20102\u2010hydroxypropylmethacrylamide) (pHPMA) as hydrophilic shell, which are crosslinked\u2014or not\u2014in the hydrophobic core is comparatively analyzed. Both types of micelles are incubated with human blood plasma and separated by asymmetrical flow field\u2010flow fractionation (AF4). Their size is determined by dynamic light scattering and proteins within the micellar fraction are characterized by gel electrophoresis and quantified by liquid chromatography\u2010high\u2010resolution mass spectrometry\u2010based label\u2010free quantitative proteomics. The analyses reveal only very low amounts of plasma proteins associated with the micelles. Notably, no significant enrichment of plasma proteins is detectable for core\u2010crosslinked micelles, while noncrosslinked micelles show a significant enrichment of plasma proteins, indicative of protein corona formation. The results indicate that preventing the reorganization of micelles (equilibrium with unimers) by core\u2010crosslinking is crucial to reduce the interaction with plasma proteins.<\/jats:p>","DOI":"10.1002\/mabi.202000414","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T03:24:59Z","timestamp":1612754699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Effect of Core\u2010Crosslinking on Protein Corona Formation on Polymeric Micelles"],"prefix":"10.1002","volume":"21","author":[{"given":"Irina","family":"Alberg","sequence":"first","affiliation":[{"name":"Department of Chemistry Johannes Gutenberg University Mainz  Duesbergweg 10\u201014 55099 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Chemistry Johannes Gutenberg University Mainz  Duesbergweg 10\u201014 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