title: The biomolecular corona is retained during nanoparticle uptake and protects the cells from the damage induced by cationic nanoparticles until degraded in the lysosomes.
abstract: Nanoparticles have unique capacities of interacting with the cellular machinery and entering cells. To be able to exploit this potential, it is essential to understand what controls the interactions at the interface between nanoparticles and cells: it is now established that nanoparticles in biological media are covered by proteins and other biomolecules forming a "corona" on the nanoparticle surface, which confers a new identity to the nanoparticles. By labelling the proteins of the serum, using positively-charged polystyrene, we now show that this adsorbed layer is strong enough to be retained on the nanoparticles as they enter cells and is trafficked to the lysosomes on the nanoparticles. There, the corona is degraded and this is followed by lysosomal damage, leading to cytosolic release of lysosomal content, and ultimately apoptosis. Thus the corona protects the cells from the damage induced by the bare nanoparticle surface until enzymatically cleared in the lysosomes.
  
  
  BACKGROUND
  This study investigates the effects of protein corona that normally forms on the surface of nanoparticles during in vivo use, describing the steps of intracellular processing of such particles, to enhance our understanding of how these particles interact with the cellular machinery.
authors: Centre for BioNano Interactions, School of Chemistry and Chemical Biology & UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland; Department of Cellular and Molecular Biology, CIB, CSIC, Ramiro de Maeztu 9, E-28040 Madrid, Spain.
authors: Fengjuan
authors: F
authors: Wang
authors: Lu
authors: L
authors: Yu
authors: Marco P
authors: MP
authors: Monopoli
authors: Peter
authors: P
authors: Sandin
authors: Eugene
authors: E
authors: Mahon
authors: Anna
authors: A
authors: Salvati
authors: Kenneth A
authors: KA
authors: Dawson
mesh_terms: D000327:Adsorption; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism; D002412:Cations / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D053758:Nanoparticles / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D010539:Permeability; D059748:Proteolysis; D013499:Surface Properties
chemical_list: D001798:Blood Proteins; D002412:Cations; D010447:Peptide Hydrolases
keywords: Amino modified polystyrene; Corona; Ctrl; DMEM; Dulbecco’s Modified Eagle’s Medium; GAPDH; Glyceraldehyde 3-phosphate dehydrogenase; LAMP-1; Lysosomal membrane permeabilization; NPs; PBS; PI; PS-N(CH(3))(3)(+); PS-NH(2)-B; PS-NH(2)-F; PS-NH(2)-S; SDS-PAGE; amino modified polystyrene from Bangs Lab; amino modified polystyrene from Bangs Lab fluorescently labelled with Alexa 488 dye; amino modified polystyrene from Sigma; cDMEM; complete DMEM; lysosomal associated membrane protein-1; nanoparticles; phosphate buffered saline; propidium iodide; quaternary amino modified polystyrene; serum free DMEM; sfDMEM; sodium dodecyl sulfate polyacrylamide gel electrophoresis; untreated control