Biomedical Engineering Reference
In-Depth Information
cleared from the blood and are excreted, whereas others are retained in tissues [106, 107].
Another problem relates to the delivery of the antisense probes to the cytoplasm of
the cell. many methods have been reported for imaging RNA in cell culture that rely
on the addition of some cell permeabilizing agent or physical method for transient
disruption of the cell membrane to allow the probes to enter the cells [108, 109].
most of these agents, however, would be unsuitable for use in humans. This is where
nanoparticles (NP) have a distinct advantage as a delivery agent [110-112]. NP can
be engineered to have a size that is retained by the circulatory system and can be
adorned with antisense probes along with a wide array of functionality to enable
targeting to a specific tissue and to gain intracellular entry (Fig. 13.8).
Among the first types of agents for antisense delivery were cationic lipids, such as
Lipofectamine [113-117]. These cationic agents can assemble into cationic micelles
and liposomes that can bind negatively charged antisense imaging agents, or to
hybrids formed between an uncharged ODN analog, such as a PNA, and a partially
complementary ODN (Fig. 13.8a). The antisense agents can also be encapsulated
within liposomes (Fig. 13.8b), and these complexes can either fuse directly with the
outer cellular membranes or be endocytosed. more recently, naturally occurring exo-
somes have been investigated for the delivery of siRNA [118, 119]. cationic delivery
(a)
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(b)
HS
-S
Au
Au
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-CONH
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Bioreduction
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SH
fIgure 13.8
general methods for ligating or sequestering antisense agents to nanocarri-
ers. From top to bottom: (a) direct electrostatic association with a cationic nanoparticle or lipid
or via hybridization of a neutral antisense agent to a negatively charged complementary olig-
omer, (b) entrapment in a liposome or exosome, (c) thiol-gold bond formation, (d) amide bond
formation, and (e) bioreductively cleavable disulfide bond formation.
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