Biomedical Engineering Reference
In-Depth Information
transfection efficacy in HepG2 and HeLa cells due to the specific interactions
between transferrin ligands and their receptors on tumor cells.
N-Acetylglucosamine (GlcNAc)-conjugated agents can be targeted to the
vimentin- and desmin-expressing cells and tissues. Kim et al. synthesized
GlcNAc grafted PEI conjugates that showed reduced cytotoxicity and
significant transfection efficiency in vimentin-expressing 293FT and HeLa
cells.
44
This gene-delivery system could be used to target various vimentin-
expressing cells such as fibroblasts and tumor cells.
Boronic acid was found to selectively bind oligo- or polysaccharides such as
heparin and glycoproteins. Peng et al. synthesized phenylboronic acid-
modified PEI by coupling 1800 Da PEI with 4-(bromomethyl)phenylboronic
acid
d
n
4
y
3
n
g
|
3
molecules.
45
This
compound
showed
obviously
higher
transfection
efficiency
in
HepG2
cells
compared
to
25 kDa
PEI,
attributed
to
the
interaction between boronic acid and carbohydrate on the cell surface.
4.2.3 Other Polyethylenimine Derivatives
In addition to improved low-toxicity and tumor-targeting capability, various
efforts have been made to enhance the transfection efficiency of PEI. Yang
et al. reported that polyurethane-short-branch polyethylenimine (PU-PEI)
exhibited high transfection efficiency with relatively low cytotoxicity in vitro
and in vivo.
46
As a therapeutic delivery vehicle, PU-PEI-mediated miR145
delivery to glioblastomas-CD133+ significantly inhibited their tumorigenic and
cancer stem cell-like abilities.
Swami et al. reacted butane-1,4-diol diglycidyl ether (BDE)-crosslinked PEI
(25 kDa) nanoparticles with varying proportions of a novel linker, 2-(N-1-
tritylimidazol-4-yl)-N-(6-glycidyloxyhexyl)acetamide, to yield PN-g-imidazolyl
nanoparticles with improved transfection efficiency.
47
Recently, Goyal et al.
showed the effect of imidazole grafting through an epoxy end-based linker on
BDE-crosslinked PEI nanoparticles.
48
It was found that introduction of
imidazole groups resulted in enhancement of the transfection efficiency of
crosslinked nanoparticles, which was higher than PEI and commercial
transfection reagents in vitro and in vivo. They also synthesized a series of
linear PEI nanoparticles by crosslinking with BDE that exhibited excellent
transfection efficiency in comparison with 25 kDa PEI and Lipofectamine.
49
Morris et al. synthesized arginine-modified oligo(alkylaminosiloxane)-
conjugated PEI by simple reproducible reaction methods.
50
These nanopar-
ticles were found to exhibit higher cell viability and gene transfection efficiency
than 25 kDa PEI in KB cell lines. They found that the enhanced transfection
was due to the existence of a uniformly spaced arginine moiety via
oligoalkylaminosiloxane arms, which could promote the cellular uptake by
multiple pathways and subsequent entry into the nucleus.
Some studies have characterized lyophilized complexes and have investi-
gated the applicability of dry powder aerosols for pulmonary gene delivery.
Pfeifer et al. investigated PEI/pDNA dry powder aerosols as novel gene
