title: The mechanisms of surface chemistry effects of mesoporous silicon nanoparticles on immunotoxicity and biocompatibility.
abstract: Despite steadily increasing insights on the biocompatibility of PSi nanoparticles (NPs), an extensive biosafety study on the immune and red blood cells (RBCs) is still lacking. Herein, we evaluated the impact of the PSi NPs' surface chemistry on immune cells and human RBCs both in vitro and in vivo. Negatively charged hydrophilic and hydrophobic PSi NPs caused less ATP depletion and genotoxicity than the positively charged amine modified hydrophilic PSi NPs, demonstrating the main role of PSi NPs' surface charge on the immunocompatibility profile. Furthermore, cells with lower metabolic activity, longer doubling time, and shorter half-life were more sensitive to the concentration- and time-dependent toxicity in the following order: T-cells ≈ monocytes > macrophages ≈ B-cells. RBC hemolysis and imaging assay revealed a significant correlation between the surface chemistry, the amount of the PSi NPs adsorbed on the cell surface and the extent of morphological changes. The in vivo results showed that despite mild renal steatosis, glomerular degeneration, hepatic central vein dilation and white pulp shrinkage in spleen, no notable changes were observed in the serum level of biochemical and hematological factors. This study is a comprehensive demonstration of the mechanistic direct and indirect genotoxicity effects of PSi NPs, elucidating the most influencing properties for the PSi NPs' design.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Shahbazi
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hamidi
authors.forename: Ermei M
authors.initials: EM
authors.lastname: Mäkilä
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.forename: Patrick V
authors.initials: PV
authors.lastname: Almeida
authors.forename: Martti
authors.initials: M
authors.lastname: Kaasalainen
authors.forename: Jarno J
authors.initials: JJ
authors.lastname: Salonen
authors.forename: Jouni T
authors.initials: JT
authors.lastname: Hirvonen
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D002460:Cell Line; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D064347:Microscopy, Electrochemical, Scanning; D053758:Nanoparticles / Q000009:adverse effects* / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012825:Silicon / Q000737:chemistry*
chemical_list: D012825:Silicon
keywords: Erythrocytes; Genotoxicity; Hemocompatibility; Histopathology; Immune cells; Porous silicon nanoparticles