Biomedical Engineering Reference
In-Depth Information
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Figure 9.4
Preparation of cationic shell-crosslinked knedel-like nanoparticles.
10
transfection of mammalian cells. In this work, a robust synthetic nanostructure
was designed for the effective packaging of DNA and it was shown to be
an efficient agent for cell transfection. An amphiphilic block copolymer,
poly(acrylamidoethylamine)-b-polystyrene (PAEA
128
-b-PS
40
), was synthe-
sized, micellized in water, and shell-crosslinked using a diacid-derivatized
crosslinker. A series of discrete complexes of the cSCKs with plasmid DNA
(pDNA) was able to be formed over a broad range of polymer amine:pDNA
phosphate ratios (N/P ratios), 2:1-20:1. Intracellular delivery of a splice-
correcting phosphorothioate and genetic material, respectively, by the cSCKs
led to much higher transfection efficiency than the performance of poly
(amidoamine) (PAMAM) dendrimers.
Dual peptide nucleic acid- and peptide-functionalized shell-crosslinked
nanoparticles were also designed by Wooley et al.
11
to target mRNA toward
the diagnosis and treatment of acute lung injury. A well-designed amphiphilic
block graft copolymer (Figure 9.5) was synthesized and used as the building
blocks for the formation of well-defined SCKs, which were prepared by a series
of robust, efficient, and versatile synthetic steps as indicated in Figure 9.6. The
multifunctional biosynthetic hybrid nanostructures had potential utility in the
recognition and inhibition of mRNA sequences for inducible nitric oxide
synthase (iNOS), which are overexpressed at sites of inflammation, such as in
cases of acute lung injury.
Lee et al.
12
reported a robust CSC micelle bearing redox-responsive shell-
specific crosslinks as a carrier of docetaxel (DTX) for cancer therapy, as shown
in Figure 9.7. The polymer micelles of poly(ethylene glycol)-b-poly(
L
-lysine)-b-
poly(
L
-phenylalanine) (PEG-PLys-PPhe) in the aqueous phase provided the
three
distinct
functional
domains:
the
PEG
outer
corona
for
prolonged
