title: Proper design of silica nanoparticles combines high brightness, lack of cytotoxicity and efficient cell endocytosis.
abstract: Silica-based luminescent nanoparticles (SiNPs) show promising prospects in nanomedicine in light of their chemical properties and versatility. In this study, we have characterized silica core-PEG shell SiNPs derivatized with PEG moieties (NP-PEG), with external amino- (NP-PEG-amino) or carboxy-groups (NP-PEG-carbo), both in cell cultures as well as in animal models. By using different techniques, we could demonstrate that these SiNPs were safe and did not exhibit appreciable cytotoxicity in different relevant cell models, of normal or cancer cell types, growing either in suspension (JVM-2 leukemic cell line and primary normal peripheral blood mononuclear cells) or in adherence (human hepatocarcinoma Huh7 and umbilical vein endothelial cells). Moreover, by multiparametric flow cytometry, we could demonstrate that the highest efficiency of cell uptake and entry was observed with NP-PEG-amino, with a stable persistence of the fluorescence signal associated with SiNPs in the loaded cell populations both in vitro and in vivo settings suggesting this as an innovative method for cell traceability and detection in whole organisms. Finally, experiments performed with the endocytosis inhibitor Genistein clearly suggested the involvement of a caveolae-mediated pathway in SiNP endocytosis. Overall, these data support the safe use of these SiNPs for diagnostic and therapeutic applications.
authors.affiliation: Department of Chemistry G. Ciamician, University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Rampazzo
authors.forename: Rebecca
authors.initials: R
authors.lastname: Voltan
authors.forename: Luca
authors.initials: L
authors.lastname: Petrizza
authors.forename: Nelsi
authors.initials: N
authors.lastname: Zaccheroni
authors.forename: Luca
authors.initials: L
authors.lastname: Prodi
authors.forename: Fabio
authors.initials: F
authors.lastname: Casciano
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
authors.forename: Paola
authors.initials: P
authors.lastname: Secchiero
mesh_terms: D000818:Animals; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009360:Neoplastic Cells, Circulating; D011092:Polyethylene Glycols / Q000737:chemistry; D012235:Rhodamines / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*; D014183:Transplantation, Heterologous
chemical_list: D012235:Rhodamines; D011092:Polyethylene Glycols; D012822:Silicon Dioxide