Biomedical Engineering Reference
In-Depth Information
encoding Bcl-2 protein, which is the main player for nonpump resistance. By
delivering Dox and Bcl-2 siRNA simultaneously into cancer cells, the Bcl-2
siRNA could effectively silence the Bcl-2 mRNA and significantly suppress the
nonpump resistance and substantially enhance the anticancer activity of Dox.
It was also suggested that the Dox delivered by MSNs exhibited minimal prema-
ture release in the extracellular environment, which can greatly reduce its side
effects. Furthermore, the Dox was primarily localized in perinuclear region after
internalization, possibly bypassing the pump resistance and further enhancing the
cytotoxicity.
Chen et al. fabricated fluorescent silica nanotubes with an inner diameter of
hundreds of nanometers for gene delivery (Chen et al.
2005b
). The hollow silica
nanotubes were synthesized by a sol-gel reaction using an anodic aluminium oxide
membrane as a template. After modification of the inner surface of the silica nano-
tubes with amine groups, CdSe-ZnS nanoparticles with either green or red fluores-
cence that were stabilized with mercaptoacetic acid, were decorated on the inner
surface of the silica nanotubes through electrostatic interactions between the posi-
tively charged amine groups and negatively charged QDs. The subsequent amine-
modification of the inner surface of the silica nanotubes made it possible to
incorporate DNA molecules inside the fluorescent silica nanotubes. The transfec-
tion of pDNA-loaded nanotubes in COS-7 cells resulted in successful GFP expres-
sion. Additionally, the cytoplasmic existence of nanotubes was confirmed by
imaging using confocal laser scanning microscopy (CLSM).
6.5
Multifunctional Nanoparticles Based on Lipids
While nanomaterials such as magnetic/gold nanoparticles and QDs allow the real-
time tracking and ultrastructural localization of siRNA/DNA delivery systems,
combining drug delivery and gene therapy in one particle has the potential to
enhance the transfection efficiency or to achieve a synergistic/combined effect of
drug and gene therapies (Malone et al.
1994
; Zhang et al.
2001
; Kishida et al.
2003
;
Janat-Amsbury et al.
2004
).
By co-delivering inflammatory suppressors and pDNA through liposomes,
Huang and coworkers have developed a non-immunostimulatory gene vector (Liu
et al.
2004
). To this end, many inflammatory suppressors, such as glucocorticoids,
nonsteroidal anti-inflammatory drugs (NSAIDs), NF-kB inhibitor, and tetrandrine
(a natural compound from an herbal medicine), could be encapsulated into the
cationic liposomes for form the new lipoplexes (cationic liposome/inflammatory
suppressor/DNA). The DNA and suppressor could be co-delivered to an individual
immune cell where the cytokines are produced. The inflammatory suppressor will
be released from the vector in the cytoplasm and interrupt the cytokine production
by inhibiting NF-kB at one or multiple activation steps of the signaling pathway.
Through this way, the inflammatory toxicity induced by cationic lipids and CpG
motif of pDNA can be largely reduced.
Search WWH ::
Custom Search