Biomedical Engineering Reference
In-Depth Information
been shown to protect loaded DNA against denaturation and have potential for use as
nonviral gene delivery carriers.
Shah
et al
. [13] designed a strategy to influence signaling pathways and manipulate cell
function, including stem-cell differentiation. They established an intracellular protein
delivery through application of SiNP. They functionalized SiNP with
n
-octadecyltrime-
thoxysilane to adjust specifically targeted cell-signaling proteins. The protein (GFP-
FRATtide)-SiNP conjugates were delivered efficiently to the cytosol of human embryonic
kidney cells and rat NSCs. This uptake impacted the Wnt signaling cascade, which lead to
an elevation of β-catenin levels attributed to GSK-3b inhibition. Accumulation of β-catenin
resulted in increased transcription of Wnt target genes, such as c-MYC, which guides the
cell to actively proliferate and remain in an undifferentiated state. Therefore, in their study
functional proteins operated
in vitro
intracellular delivery by means of a nanocarrier that
acted as protein signals and regulated signaling pathways.
Solanki
et al
. [52] successfully nanoengineered the delivery of siRNA for enhanced
differentiation of NSCs by means of a self-assembled SiNP monolayer coated with
extracellular matrix proteins. This nanocarrier improved cytotoxicity and eliminated
undesirable side-effects of other carriers in the delivery of siRNA into stem cells. They
have stated that while in conventional methods such as solution-mediated delivery or
forwarded transfection, exogenous chemical materials are generally required to enhance
cellular internalization of the siRNA (cationic lipids such as Lipofectamine™ 2000 and
cationic polymers such as PEI), these exogenous materials are somehow cytotoxic and
subsequently need to be removed after a certain incubation time. To overcome the above-
mentioned limitations they have proposed a delivery platform to transfect stem cells
more efficiently. The effectiveness of this delivery platform was proven because stem
cells only took up siRNAs, and not SiNP, on the surface of the platform. Therefore, this
siRNA delivery may potentially help to overcome one of the critical barriers in stem-cell-
based tissue engineering.
Silver Nanoparticles
Silver nanoparticles have been used in antibacterial materials and surfaces. Recently, the
possibility of their use in wound dressing, surgical instruments, and bone-substitute bioma-
terials has been an interesting area of investigation. Silver nanoparticles have few potential
cytotoxic and genotoxic effects in mammalian cells such as hMSCs [53].
Greulich
et al
. [54] conducted a study to evaluate the uptake and intracellular distribution
of silver nanoparticles in hMSCs. They hypothesized that biomaterial silver nanoparticles
might come into close contact with body tissues, including hMSCs. These researchers incu-
bated hMSCs in the presence and absence of different concentrations of silver nanoparticles.
They found that silver agglomerates mainly co-localized with late endosomal-lysosomal
structures, but not in the cell nucleus, the endoplasmic reticulum, or Golgi complex. Based
on previous studies and their experiment they noticed that the uptake of cells was size
dependent.
Calcium Phosphate Nanoparticles
Calcium phosphate nanoparticles (CPNP) have shown potential as nonviral vectors for gene
delivery. Calcium can form ionic complexes with phosphates on the nucleic acid backbone of
plasmid DNA by the electrostatic interaction between the positively charged Ca
2+
and the
negatively charged nucleic acid.
Yang
et al
. [55] induced bone morphogenetic protein 2 transfection in rat dental pulp stem
cells (rDPSCs) using CPNP as gene nanocarriers. They also investigated the behavior of
