title: Transport across the cell-membrane dictates nanoparticle fate and toxicity: a new paradigm in nanotoxicology.
abstract: The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions.
authors: Center for Advanced Biomaterials for Health Care@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125 Napoli, Italy.
authors: Daniela
authors: D
authors: Guarnieri
authors: Stefania
authors: S
authors: Sabella
authors: Ornella
authors: O
authors: Muscetti
authors: Valentina
authors: V
authors: Belli
authors: Maria Ada
authors: MA
authors: Malvindi
authors: Sabato
authors: S
authors: Fusco
authors: Elisa
authors: E
authors: De Luca
authors: Pier Paolo
authors: PP
authors: Pompa
authors: Paolo A
authors: PA
authors: Netti
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects*; D004058:Diffusion; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D051379:Mice; D013347:Subcellular Fractions / Q000737:chemistry*