title: Protein corona acts as a protective shield against Fe3O4-PEG inflammation and ROS-induced toxicity in human macrophages.
abstract: Protein corona (PC) is the main biological entity of initial cell interaction and can define the toxicological response to Fe3O4 nanoparticles (IONP). Polymer coating to IONP, polyethilenglycol (PEG) and polyvinylpyrrolidone (PVP), is a widely accepted strategy to prevent toxicity and avoid excessive protein binding. The aim of this study was to assess the role of PC as a potential protector for ROS-induced cytotoxicity and pro-inflammatory response in THP-1 macrophages (exposed to three different IONP: bare, PVP or PEG coated). Cells were exposed to either IONP in RPMI-1640 media or IONP with a preformed human PC. All three IONP showed cytotoxic effects, which in the presence of PC was abolished. IONP-PEG exposure significantly increased ROS, mitochondrial dysfunction and pro-inflammatory cytokines release (IL-1β and TNF-α). PC presence on IONP-PEG promoted a decrease in ROS and prevented cytokine secretion. Also, presence of PC reduced cell uptake for IONP-bare, but had no influence on IONP-PVP or IONP-PEG. Hence, the reduction in IONP-PEG cytotoxicity can be attributed to PC shielding against ROS generation and pro-inflammatory response and not a differential uptake in THP-1 macrophages. The presence of the PC as a structural element of NP biological entity provides in vivo-relevant conditions for nanosafety testing.
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), México Distrito Federal, Mexico.
authors.forename: V
authors.initials: V
authors.lastname: Escamilla-Rivera
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), México Distrito Federal, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Uribe-Ramírez
authors.affiliation: Unidad de Microscopía Electrónica (LaNSE), CINVESTAV-IPN, Mexico.
authors.forename: S
authors.initials: S
authors.lastname: González-Pozos
authors.affiliation: Namur Nanosafety Centre (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium; Research Centre for the Physics of Matter and Radiation (PMR), University of Namur, Namur, Belgium.
authors.forename: O
authors.initials: O
authors.lastname: Lozano
authors.affiliation: Namur Nanosafety Centre (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium; Research Centre for the Physics of Matter and Radiation (PMR), University of Namur, Namur, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Lucas
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), México Distrito Federal, Mexico. Electronic address: avizcaya@cinvestav.mx.
authors.forename: A
authors.initials: A
authors.lastname: De Vizcaya-Ruiz
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D005290:Ferric Compounds / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D000066970:Protein Corona; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020099:Coated Materials, Biocompatible; D005290:Ferric Compounds; D053583:Interleukin-1beta; D015850:Interleukin-6; D000066970:Protein Corona; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C000499:ferric oxide; D011092:Polyethylene Glycols; D011205:Povidone
keywords: Fe(3)O(4) nanoparticles; Inflammation; Nanotoxicology; Protein corona