Biomedical Engineering Reference
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have been successfully assembled with therapeutic nanocarriers for
targeted RNAi.
5.3.2.1
CD4 RNA aptamer-functionalized pRNA-nanoparticles
The anti-CD4 RNA aptamers also have been fused into a
multifunctional nanoparticle for targeted siRNA delivery. Through
the interaction of two interlocking loops, bacterial virus phi29 DNA
packaging RNA (pRNA) molecules are able to form dimers, trimers,
hexamers, and patterned superstructures [84]. Guo and his co-
workers have creatively taken advantage of this self-assembly
property to fabricate pRNA-based nanoparticles with a variety
of structures and shapes [85]. As an ideal RNA building block for
bottoms-up assembly, pRNAs can be covalently fused with thera-
peutic agents, targeting ligands, or imaging agents and subsequently
self-assemble into multifunctional nanopaticles, allowing aptamer-
directed cell-specific gene silencing and drug tracking. In contrast
to the average size of a normal single siRNA molecule that is well
below 10 nm, aptamer-functionalized pRNA nanoparticles (dimers
or trimers) have sizes ranging between 20 and 40 nm, which have
improved circulation time and biodistribution
in vivo
.
5.3.2.2
PSMA RNA aptamer-functionalized polymer
nanocarriers
During the chemical synthesis of nucleic acids, various functional
groups can be readily incorporated into the aptamers to function-
alize them as nanocarriers. For example, synthetic aptamers
containing a 5
group can be conjugated with a terminal
carboxylic acid on the surface of nanoparticles using carbodiimide
coupling chemistry. Using this method Farokhzad and colleagues
[86] reported the first example of a PSMA aptamer-functionalized
poly(lactic acid)-block-polyethylene glycol copolymer (PLA-b-PEG
nanoparticles) for targeted delivery of rhodamine-labeled dextran.
After that, various nanoparticles, including PLGA-b-PEG [87-89]
and super-paramagnetic iron oxide [90], have been functionalized
with cell-specific aptamers.
′
-NH
2
′
-modified PSMA aptamer was chemically
coupled with a branched polyethyleneimine-grafted polyethylene
glycol polymer (PEI-PEG) that serves as a vehicle for shRNA
delivery [91]. Moreover, aptamers generally have a single 5
Recently, a 5
-NH
2
′
-CG-3
′
sequence in its predicted double-stranded stem region, which is
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