Mesoporous silica- and silicon-based materials ... - Helda - Helsinki.fi

The shape and surface properties of the mesoporous silica materials also affect their
internalization and cytotoxicity. The effects vary from toxic to non-toxic depending on the
cell lines and surface treatments used. Recently, the uptake of silica nanoparticles into
various human, rat and murine cells was reported with sizes ranging from 40 nm to 5 µm
(Chen and von Mikecz, 2005). The studies were performed with particle suspensions of 25
µg/ml, and penetration of the particles into the nucleus was detected only for sizes of 40-
70 nm, while all the particles were able to pass the cell membrane into the cytoplasm. The
particles induced formation of protein aggregates in the nucleoplasm, which is harmful for
normal cell functions. Another study showed internalization of mesoporous silica
nanoparticles (~110 nm) containing attached fluorescein dye into 3T3-L1 fibroblast cells’
cytoplasms after one hour of exposure with no evidence of cellular damage (Lin et al.,
2005). The shape of the particles also affected the internalization extent and rate into A375
human melanoma cells (Huang et al., 2010). Mesoporous silica particles with higher
aspect ratio (i.e. length/width) had a stronger effect on the cell functions than the rounder
particles in terms of, e.g. cell proliferation and apoptosis. Toxicity studies of MCM-41
particles and surface treated counterparts with human neuroblastoma cells (SK–N–SH)
suggested that decreasing the surface area of the material improves safety, as well as the
surface functionalization of the material (Di Pasqua et al., 2008). Chang and co-workers
showed that cancer epithelial cells that proliferate faster than normal fibroblasts are less
sensitive to silica exposures (Chang et al., 2007). The same study also suggested that the
silica nanoparticles exhibit toxicity at concentrations above 138 µg/ml, although the
cytotoxicity of silica could be reduced by surface treatment with chitosan. The increasing
surface charge of MCM-41 nanoparticles (~100 nm) improved to some extent their uptake
into both human mesenchymal stem cells and 3T3-L1 fibroblast cells (Chung et al., 2007).
The particles with various surface charges did not affect the cell functions. Similar results
have also been obtained with surface-functionalized MCM-41 in human cervical cancer
cells (Slowing et al., 2006).
The in vitro safety studies with mesoporous silicon/silica-based materials are variable
with regard to the studied materials, cell lines and treatments, as summarized in Table 2.
Few critical parameters related to the in vitro cytotoxicity of mesoporous silica and PSi
have been identified (Figure 5). The in vivo response to the materials will be discussed in
the following chapter.
2.2.3.2 In vivo studies
Mesoporous silicon has been recognized as a non-toxic and feasible material for drug
delivery in several in vivo studies. Since the early investigations using implants of large
PSi disks (Bowditch et al., 1999; Rosengren et al., 2000), materials ranging from nano- to
micron-sizes have been administered orally, subcutaneously and intravenously to rodents
in order to access the safety information of plain or surface modified PSi (Park et al.,
2009; Tanaka et al., 2010a, 2010b; Bimbo et al., 2010; Chiappini et al., 2011).
THCPSi (average particle size of 142 nm) did not cross the intestinal cell wall after
oral administration in rats (Bimbo et al., 2010). This makes the material a promising
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