TY - JOUR
T1 - Biocompatibility of Amine-Functionalized Silica Nanoparticles
T2 - The Role of Surface Coverage
AU - Hsiao, I. Lun
AU - Fritsch-Decker, Susanne
AU - Leidner, Arnold
AU - Al-Rawi, Marco
AU - Hug, Vanessa
AU - Diabaté, Silvia
AU - Grage, Stephan L.
AU - Meffert, Matthias
AU - Stoeger, Tobias
AU - Gerthsen, Dagmar
AU - Ulrich, Anne S.
AU - Niemeyer, Christof M.
AU - Weiss, Carsten
N1 - Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/3/8
Y1 - 2019/3/8
N2 - Here, amorphous silica nanoparticles (NPs), one of the most abundant nanomaterials, are used as an example to illustrate the utmost importance of surface coverage by functional groups which critically determines biocompatibility. Silica NPs are functionalized with increasing amounts of amino groups, and the number of surface exposed groups is quantified and characterized by detailed NMR and fluorescamine binding studies. Subsequent biocompatibility studies in the absence of serum demonstrate that, irrespective of surface modification, both plain and amine-modified silica NPs trigger cell death in RAW 264.7 macrophages. The in vitro results can be confirmed in vivo and are predictive for the inflammatory potential in murine lungs. In the presence of serum proteins, on the other hand, a replacement of only 10% of surface-active silanol groups by amines is sufficient to suppress cytotoxicity, emphasizing the relevance of exposure conditions. Mechanistic investigations identify a key role of lysosomal injury for cytotoxicity only in the presence, but not in the absence, of serum proteins. In conclusion, this work shows the critical need to rigorously characterize the surface coverage of NPs by their constituent functional groups, as well as the impact of serum, to reliably establish quantitative nanostructure activity relationships and develop safe nanomaterials.
AB - Here, amorphous silica nanoparticles (NPs), one of the most abundant nanomaterials, are used as an example to illustrate the utmost importance of surface coverage by functional groups which critically determines biocompatibility. Silica NPs are functionalized with increasing amounts of amino groups, and the number of surface exposed groups is quantified and characterized by detailed NMR and fluorescamine binding studies. Subsequent biocompatibility studies in the absence of serum demonstrate that, irrespective of surface modification, both plain and amine-modified silica NPs trigger cell death in RAW 264.7 macrophages. The in vitro results can be confirmed in vivo and are predictive for the inflammatory potential in murine lungs. In the presence of serum proteins, on the other hand, a replacement of only 10% of surface-active silanol groups by amines is sufficient to suppress cytotoxicity, emphasizing the relevance of exposure conditions. Mechanistic investigations identify a key role of lysosomal injury for cytotoxicity only in the presence, but not in the absence, of serum proteins. In conclusion, this work shows the critical need to rigorously characterize the surface coverage of NPs by their constituent functional groups, as well as the impact of serum, to reliably establish quantitative nanostructure activity relationships and develop safe nanomaterials.
KW - cytotoxicity
KW - macrophages
KW - silica nanoparticles
KW - surface-characterization
KW - surface-functionalization
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U2 - 10.1002/smll.201805400
DO - 10.1002/smll.201805400
M3 - Article
C2 - 30721573
AN - SCOPUS:85061041387
SN - 1613-6810
VL - 15
JO - Small
JF - Small
IS - 10
M1 - 1805400
ER -