title: Modification of the protein corona-nanoparticle complex by physiological factors.
abstract: Nanoparticle (NP) effects in a biological system are driven through the formation and structure of the protein corona-NP complex, which is dynamic by nature and dependent upon factors from both the local environment and NP physicochemical parameters. To date, considerable data has been gathered regarding the structure and behavior of the protein corona in blood, plasma, and traditional cell culture medium. However, there exists a knowledge gap pertaining to the protein corona in additional biological fluids and following incubation in a dynamic environment. Using 13nm gold NPs (AuNPs), functionalized with either polyethylene glycol or tannic acid, we demonstrated that both particle characteristics and the associated protein corona were altered when exposed to artificial physiological fluids and under dynamic flow. Furthermore, the magnitude of observed behavioral shifts were dependent upon AuNP surface chemistry. Lastly, we revealed that exposure to interstitial fluid produced protein corona modifications, reshaping of the nano-cellular interface, modified AuNP dosimetry, and induction of previously unseen cytotoxicity. This study highlights the need to elucidate both NP and protein corona behavior in biologically representative environments in an effort to increase accurate interpretation of data and transfer of this knowledge to efficacy, behavior, and safety of nano-based applications.
authors.affiliation: Molecular Bioeffects Branch, Bioeffects Division, Human Effectiveness Directorate, 711 Human Performance Wing, Air Force Research Laboratory, Wright Patterson AFB, 2729 R. St, Bldg 837, Dayton, OH, 45433, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Braun
authors.affiliation: Molecular Bioeffects Branch, Bioeffects Division, Human Effectiveness Directorate, 711 Human Performance Wing, Air Force Research Laboratory, Wright Patterson AFB, 2729 R. St, Bldg 837, Dayton, OH, 45433, USA.
authors.forename: Madeleine C
authors.initials: MC
authors.lastname: DeBrosse
authors.affiliation: Molecular Bioeffects Branch, Bioeffects Division, Human Effectiveness Directorate, 711 Human Performance Wing, Air Force Research Laboratory, Wright Patterson AFB, 2729 R. St, Bldg 837, Dayton, OH, 45433, USA.
authors.forename: Saber M
authors.initials: SM
authors.lastname: Hussain
authors.affiliation: Department of Chemical and Materials Engineering, University of Dayton, 524 Kettering Laboratories, 300 College Park, Dayton, OH 45469, USA. Electronic address: kcomfort1@udayton.edu.
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Comfort
mesh_terms: D002460:Cell Line; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D013634:Tannins / Q000737:chemistry
chemical_list: D020099:Coated Materials, Biocompatible; D013634:Tannins; D011092:Polyethylene Glycols; D006046:Gold; C000595209:polyethylene glycol 1000
keywords: Cytotoxicity; Dynamic flow; Gold nanoparticle; Interstitial fluid; Nano-cellular interface; Tannic acid