title: Surface functionalization of silica nanoparticles supports colloidal stability in physiological media and facilitates internalization in cells.
abstract: The influence of the surface functionalization of silica particles on their colloidal stability in physiological media is studied and correlated with their uptake in cells. The surface of 55 ± 2 nm diameter silica particles is functionalized by amino acids or amino- or poly(ethylene glycol) (PEG)-terminated alkoxysilanes to adjust the zeta potential from highly negative to positive values in ethanol. A transfer of the particles into water, physiological buffers, and cell culture media reduces the absolute value of the zeta potential and changes the colloidal stability. Particles stabilized by L-arginine, L-lysine, and amino silanes with short alkyl chains are only moderately stable in water and partially in PBS or TRIS buffer, but aggregate in cell culture media. Nonfunctionalized, N-(6-aminohexyl)-3-aminopropyltrimethoxy silane (AHAPS), and PEG-functionalized particles are stable in all media under study. The high colloidal stability of positively charged AHAPS-functionalized particles scales with the ionic strength of the media, indicating a mainly electrostatical stabilization. PEG-functionalized particles show, independently from the ionic strength, no or only minor aggregation due to additional steric stabilization. AHAPS stabilized particles are readily taken up by HeLa cells, likely as the positive zeta potential enhances the association with the negatively charged cell membrane. Positively charged particles stabilized by short alkyl chain aminosilanes adsorb on the cell membrane, but are weakly taken up, since aggregation inhibits their transport. Nonfunctionalized particles are barely taken up and PEG-stabilized particles are not taken up at all into HeLa cells, despite their high colloidal stability. The results indicate that a high colloidal stability of nanoparticles combined with an initial charge-driven adsorption on the cell membrane is essential for efficient cellular uptake.
authors.affiliation: Physikalische Chemie, Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany. cmgraf@chemie.fu-berlin.de
authors.forename: Christina
authors.initials: C
authors.lastname: Graf
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Irene
authors.initials: I
authors.lastname: Schütz
authors.forename: Christelle Njiki
authors.initials: CN
authors.lastname: Noufele
authors.forename: Wentao
authors.initials: W
authors.lastname: Ruan
authors.forename: Uta
authors.initials: U
authors.lastname: Posselt
authors.forename: Elena
authors.initials: E
authors.lastname: Korotianskiy
authors.forename: Daniel
authors.initials: D
authors.lastname: Nordmeyer
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Rancan
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hadam
authors.forename: Annika
authors.initials: A
authors.lastname: Vogt
authors.forename: Jürgen
authors.initials: J
authors.lastname: Lademann
authors.forename: Volker
authors.initials: V
authors.lastname: Haucke
authors.forename: Eckart
authors.initials: E
authors.lastname: Rühl
mesh_terms: D000327:Adsorption; D000596:Amino Acids / Q000737:chemistry; D001692:Biological Transport; D002021:Buffers; D003102:Colloids; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009994:Osmolar Concentration; D012821:Silanes / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry* / Q000378:metabolism*; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D002021:Buffers; D003102:Colloids; D012821:Silanes; D014867:Water; D012822:Silicon Dioxide