Biomedical Engineering Reference
In-Depth Information
trastuzumab (herceptin) was conjugated to the DNA/polycation complexes to target
tumor cells. The studies indicated that the surface functionalized complexes had up
to 20-fold higher transfection activity compared with non-cationic polymer based
gene transfer in breast cancer cells. This is a significant improvement that promises
possible chemotherapeutic applications of the DNA/polycation complexes against
cancer cells.
Studies have also indicated that the size of the NMs can significantly impact
gene transfer efficiency in vivo.
67
Optimization of particle size has been observed
to improve the clearance behavior of intravenously injected NMs as well as their
tissue distribution and therefore, the efficiency of drug or gene delivery is also
improved.
68,69
Studies have also indicated that smaller poly-(D,L-lactide-
co
-
glycolide) (PLGA) about 70 ± 2 nm in diameter carrying a pDNA exhibited
27-fold higher transfection than larger-sized NPs in the HEK-293 cell line.
67
NMs have been used for the delivery of small interfering RNA (siRNA)
as a potential therapeutic approach for genetic diseases.
53
NMs have been
used to stabilize siRNA in physiological fluids and to improve their intracel-
lular uptake.
70
Chitosan coated polyisohexylcyanoacrylate (PIHCA) NMs that
encapsulated anti-RhoA siRNA in nude mice with breast cancer showed 90%
inhibition of tumor growth without toxic effect.
71
PEI that was complexed with
siRNA (PEI-complexed siRNA) targeting the HER-2 receptor that was intra-
peritoneally injected in mice resulted in the delivery of the intact siRNA into the
tumors that exhibited reduction in tumor growth.
72,73
Today, liposomes are clinically more advanced than other NMs as drug-
delivery systems because of their inherent properties that includes biocompat-
ibility, high drug payload, and easy drug-encapsulation capability.
16,52
Barriers
to its widespread acceptability requires improved efficiency and lower cytotox-
icity which may behave toward opposite directions such that to improve effi-
ciency may require higher levels of the liposome but this level may lead to
higher toxicity. Optimization conditions may be achieved through a balance
between these two conditions. New NMs for gene-delivery systems that pro-
vide precise physical and chemical engineering of nanoscale structures have
emerged in the last few years which address these issues.
74,75
7.3.1 Gene Delivery with Inorganic NMs
Research has demonstrated that the use of AuNPs serve as excellent systems for
the delivery of genetic materials into cells.
76,77
AuNPs as gene-delivery vehicles
are especially attractive because the particles are easily conjugated with bio-
molecules
78
and allows high gene packing density that facilitates better deliv-
ery efficiency as well as improved enzymatic degradation of DNA strands.
52
In
addition, AuNPs are non-toxic and not immunogenic.
79,80
In one of the more
recent studies, liposomes and AuNPs were combined in an attempt to combine
the advantageous properties of both types of NMs, Rhim and collaborators
52
developed a lipid-DNA-AuNP (L-DNA-AuNP) hybrid-based gene-delivery
