Biomedical Engineering Reference
In-Depth Information
transfected cells when seeded on three-dimensional titanium fiber mesh scaffolds. Their
results showed that nanoparticles could protect the DNA encapsulated inside from external
DNase and release the loaded DNA in a low-acid environment.
In vitro
, nanoparticle trans-
fection was shown to be effective and either accelerated or promoted the odontogenic
differentiation of rDPSCs when cultured in three-dimesional scaffolds.
Cao
et al
. [56] have developed a CPNP that encapsulates plasmid DNA (CP-pDNA)
nanoparticles as a nonviral vector for gene delivery in MSCs. They have constructed
CPNP incorporating plasmid transforming growth factor beta 1 (TGF-β1) and evaluated
transfection efficiency, cell viability, and cytotoxicity of the CP-pDNA nanoparticles. The
prepared CP-pDNA nanoparticles have exhibited significantly lower cytotoxicity than
Lipofectamine™ 2000. The cellular uptake and transfection efficiency of the CP-pDNA
nanoparticles into the MSCs were higher than needle-like CPNP and a standard calcium
phosphate transfection kit.
In another work [57], the same group prepared plasmid DNA/CPNP (pDNA-CP) by
incorporating negative plasmid DNA-encoding TGF-β1 into CPNP in which they mixed
fibronectin and loaded pDNA-CP into collagen/CS scaffolds to construct a three-dimensional
nanoparticle gene delivery system (NGDS). They observed that the three-dimensional
NGDS could successfully transfect MSCs and induce chondrogenic differentiation
in vitro
without Dex. An advantage of this delivery system was the sustained release with an ele-
vated concentration for a relatively long period of time and high levels of transfection by
TGF-β1 compared to MSCs transfected by the Lipofectamine™ 2000 method.
Organic-Inorganic Hybrid Nanocarriers
Of note, SiNP and MNP can be hybridized with different polymers such as PEI with the
possibility for intracellular delivery of bioactive agents into stem cells.
Polymer-Magnetic Hybrid
Magnetically assisted transfection was successfully considered for efficient and rapid delivery
of gene/siRNA in different stem cells. For plasmid-based complexes, that transfection
efficiency was enhanced by conjugation of PEI complexes to MNP even without the use of
a magnetic field, as magnetic polyplexes provided a faster release of DNA into the cytosol
compared with PEI polyplexes.
Song
et al
. [58] prepared nanocarriers that consisted of PEI-coated MNPs, which were
bonded with native transactivator of transcription (TAT) peptides and plasmid DNA
encoding a luciferase reporter construct. The presence of the TAT peptide increased gene
expression fourfold both
in vitro
(human NT2 NSCs) and
in vivo
(rat spinal cord injection).
The magnetofection complexes in the cerebrospinal fluid responded to a moving magnetic
field, shifting away from the injection site and mediating transgenic expression in a remote
region. This type of combinatorial approach has implications for the development of TAT-
mediated targeted gene therapies that are controllable
in vivo
.
Schade
et al
. [59] reported a strategy for intracellular delivery of miRNA in hMSCs by
MNPs. They have designed a delivery system (DNA/PEI/MNPs) beneficial for miR delivery,
where miRs triggered their function in the cytosol close to the nucleus. This phenomenon is
justifiable due to strong biotin-streptavidin connections between PEI and MNPs compared
to DNAs where they need to pass the nuclear membrane. Polyplexes are effective vehicles to
enter the nucleus. They have used bone-marrow-derived hMSCs with miRNA to enhance
the therapeutic capacity of hMSCs in tissue engineering. The miR-335 was used, which is
encoded in the second intron of the mesoderm-specific transcript (MEST) gene and is the
