Biomaterial Database

Impact of Surface Chemistry of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles on Protein Corona Formation and Endothelial Cell Uptake, Toxicity, and Barrier Function. 2022

Daysi M Diaz-Diestra, and Teresa Palacios-Hernandez, and Yizhong Liu, and Diane E Smith, and Alexander K Nguyen, and Todor Todorov, and Patrick J Gray, and Jiwen Zheng, and Shelby A Skoog, and Peter L Goering

Division of Biology, Chemistry, and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland 20993, USA.

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) have been investigated for biomedical applications, including novel contrast agents, magnetic tracers for tumor imaging, targeted drug delivery vehicles, and magneto-mechanical actuators for hyperthermia and thrombolysis. Despite significant progress, recent clinical reports have raised concerns regarding USPION safety related to endothelial cell dysfunction; however, there is limited information on factors contributing to these clinical responses. The influence of USPION surface chemistry on nanoparticle interactions with proteins may impact endothelial cell function leading to adverse responses. Therefore, the goal of this study was to assess the effects of carboxyl-functionalized USPION (CU) or amine-functionalized USPION (AU) (approximately 30 nm diameter) on biological responses in human coronary artery endothelial cells. Increased protein adsorption was observed for AU compared with CU after exposure to serum proteins. Exposure to CU, but not AU, resulted in a concentration-dependent decrease in cell viability and perinuclear accumulation inside cytoplasmic vesicles. Internalization of CU was correlated with endothelial cell functional changes under non-cytotoxic conditions, as evidenced by a marked decreased expression of endothelial-specific adhesion proteins (eg, vascular endothelial-cadherin and platelet endothelial cell adhesion molecule-1) and increased endothelial permeability. Evaluation of downstream signaling indicated endothelial permeability is associated with actin cytoskeleton remodeling, possibly elicited by intracellular events involving reactive oxygen species, calcium ions, and the nanoparticle cellular uptake pathway. This study demonstrated that USPION surface chemistry significantly impacts protein adsorption and endothelial cell uptake, viability, and barrier function. This information will advance the current toxicological profile of USPION and improve development, safety assessment, and clinical outcomes of USPION-enabled medical products.

UI	MeSH Term	Description	Entries
D005290	Ferric Compounds	Inorganic or organic compounds containing trivalent iron.	Compounds, Ferric
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000066970	Protein Corona	A layer of protein coating adsorbed by NANOPARTICLES upon entry into PLASMA or other protein-containing biological fluids, which affects how nanoparticles are internalized by cells and cleared from the body.	Corona, Protein
D000082662	Magnetic Iron Oxide Nanoparticles	Synthesized nanoparticles related to iron oxide crystalline structures with magnetic properties useful for biomedical applications. Examples include hematite, magnetite and maghemite nanoparticles.	Hematite Nanoparticles,IONPs,Iron Oxide Nanoparticles,Maghemite Nanoparticles,Magnetic IONPs,Magnetic Iron Nanoparticles,SPIONs,Superparamagnetic Iron Nanoparticles,Superparamagnetic Iron Oxide Nanoparticles,Hematite Nanoparticle,IONP, Magnetic,IONPs, Magnetic,Iron Nanoparticle, Magnetic,Iron Nanoparticle, Superparamagnetic,Iron Oxide Nanoparticle,Maghemite Nanoparticle,Magnetic IONP,Magnetic Iron Nanoparticle,Nanoparticle, Hematite,Nanoparticle, Iron Oxide,Nanoparticle, Maghemite,Nanoparticle, Magnetic Iron,Nanoparticle, Superparamagnetic Iron,Nanoparticles, Hematite,Nanoparticles, Iron Oxide,Nanoparticles, Maghemite,Nanoparticles, Magnetic Iron,Nanoparticles, Superparamagnetic Iron,Superparamagnetic Iron Nanoparticle
D042783	Endothelial Cells	Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.	Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell
D053758	Nanoparticles	Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.	Nanocrystalline Materials,Nanocrystals,Material, Nanocrystalline,Materials, Nanocrystalline,Nanocrystal,Nanocrystalline Material,Nanoparticle