Biomedical Engineering Reference
In-Depth Information
membranes, such as in the case of pH-sensitive poly(acid) carriers and
temperature-responsive poly(electrolyte) hydrogels [62-63]. Other strate-
gies have been designed to directly overcome the plasmalemma. These in-
clude electroporation and ultrasound, where a local electric or ultrasound
pulse is exerted in the immediate post-administration period causing tran-
sient enhancement of the plasmalemma permeability [64], and biolistic
particle delivery systems, where penetration into cells is gained by means
of tungsten or gold particles that are propelled by a “gene gun” across the
plasma membrane [65]. Amphiphilic and biodegradable cationic copoly-
mers are efficient gene delivery systems, which can condense nucleic acid
and form controlled nanosized complexes. Polyamidoamine (PAMAM) and
poly[2-(dimethylamino) ethyl methacrylate] (PDMAEMA) are low toxic
polymers which have shown great potential as carriers. Polycaprolactone
(PCL) is another promising delivery system. PCL-
g
-PDMAEMA nano-
particle/DNA complexes could escape from the endosome and release their
payloads effectively in cytoplasm, which may be induced by the enhanced
interaction between the complexes and cell membrane, due to hydropho-
bic modification [66]. Small interfering RNA (siRNA) has attracted much
attention because it enables sequence-specific manipulation of expression
for multiple endogenous genes. The intracellular release of siRNA from
pluronic/poly(ethylenimine) nanocapsules was achieved by changing the
nanocapsules from a collapsed state to a swollen state using a brief cold
shock treatment [67]. Weber et al. [68] reported an amino-terminated car-
bosilane dendrimer-bound siRNA delivery system. These RNase-resistant
carbosilane/siRNA dendriplexes have a high and prolonged gene-silencing
effect, and can be safely used in serum and antibiotics containing medium,
without affecting cell viability and metabolic activity at relatively high den-
drimer concentrations. One of the most common methods used for the
systemic delivery of siRNA involves their electrostatic interaction with cat-
ionic liposomes. Self-assembled liposome-protamine-hyaluronic acid nano-
particles, modified by DSPE-PEG with conjugated ligand have been used
to overcome innate immune responses of siRNA-based therapy. The devel-
oped nanoparticle formulation has a siRNA encapsulation efficiency of 90%
and showed a reduced systemic immunotoxicity [69].
4.2 Nanomedicine and cancer
Cancer, a disease characterized by the uncontrolled growth and spread of
abnormal cells, is still the second most common cause of death in the U.S.
According to the American Cancer Society, about 571,950 Americans are
expected to die in 2011 due to cancer, and that means more than 1,500
deaths per day. Current treatments for various cancers include surgery, ra-
diation, hormone therapy, and chemotherapy. Although these conventional
therapies have improved patients' survival, they have also shown several limi-
tations. The National Cancer Institute (NCI) has identified nanotechnology
