title: Pp IX silica nanoparticles demonstrate differential interactions with in vitro tumor cell lines and in vivo mouse models of human cancers.
abstract: Protoporphyrin IX (Pp IX) silica nanoparticles, developed for effective use in photodynamic therapy (PDT), were explored in in vitro and in vivo models with the ambition to improve knowledge on the role of biological factors in the photodamage. Pp IX silica nanoparticles are found efficient at temperature with extreme metabolic downregulation, which suggest a high proportion of passive internalization. For the first time, clearance of silica nanoparticles on tumor cells is established. Cell viability assessment in six tumor cell lines is reported. In all tumor types, Pp IX silica nanoparticles are more efficient than free Pp IX. A strong fluorescence signal of reactive oxygen species generation colocalized with Pp IX silica nanoparticles, correlates with 100% of cell death. In vivo studies performed in HCT 116, A549 and glioblastoma multiforme tumors-bearing mice show tumor uptake of Pp IX silica nanoparticles with better tumor accumulation than the control alone, highlighting a high selectivity for tumor tissues. As observed in in vitro tests, tumor cell type is likely a major determinant but tumor microenvironment could more influence this differential time accumulation dynamic. The present results strongly suggest that Pp IX silica nanoparticles may be involved in new alternative local applications of PDT.
authors.affiliation: Nanobiotix SA, rue de Wattignies, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Simon
authors.forename: Corinne
authors.initials: C
authors.lastname: Devaux
authors.forename: Audrey
authors.initials: A
authors.lastname: Darmon
authors.forename: Thibault
authors.initials: T
authors.lastname: Donnet
authors.forename: Edouard
authors.initials: E
authors.lastname: Thiénot
authors.forename: Matthieu
authors.initials: M
authors.lastname: Germain
authors.forename: Jérôme
authors.initials: J
authors.lastname: Honnorat
authors.forename: Alex
authors.initials: A
authors.lastname: Duval
authors.forename: Agnès
authors.initials: A
authors.lastname: Pottier
authors.forename: Elsa
authors.initials: E
authors.lastname: Borghi
authors.forename: Laurent
authors.initials: L
authors.lastname: Levy
authors.forename: Julie
authors.initials: J
authors.lastname: Marill
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide
chemical_list: D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; C028025:protoporphyrin IX