Biomedical Engineering Reference
In-Depth Information
into cytosol for mRNA knockdown. Polymersome-mediated knockdown appears as
efficient as common cationic-lipid transfection reagents such as Lipofectamine
2000, and about half as effective as Lenti-virus after sustained selection.
Recently, we have also prepared nanosized polymersomes through self-
assembly of star-shaped PEG-
b
-PLLA block copolymers (eight-arm PEG-
b
-
PLLA) using a film hydration technique [
233
]. The polymersomes can encapsulate
FITC-labeled Dex, as model of a water-soluble macromolecular drug, into the
hydrophilic interior space. The eight-arm PEG-
b
-PLLA polymersomes showed
relatively high stability compared to that of polymersomes of linear PEG-
b
-PLLA
copolymers with the equal volume fraction. Furthermore, we have developed a
novel type of polymersome of amphiphilic polyrotaxane (PRX) composed of
PLLA-
b
-PEG-
b
-PLLA triblock copolymer and
a
-cyclodextrin (
a
-CD) [
234
]. These
polymersomes possess unique structures: the surface is covered by PRX
structures with multiple
a
-CDs threaded onto the PEG chain. Since the
a
-CDs are
not covalently bound to the PEG chain, they can slide and rotate along the PEG chain,
which forms the outer shell of the polymersomes [
235
,
236
]. Thus, the polymersomes
could be a novel functional biomedical nanomaterial having a dynamic surface.
Recently, a biomimicking self-assembly approach using polypeptides has
emerged for the preparation of functional polymersomes for in vivo use. The
formation of fully polypeptide-based polymersome was first demonstrated using
poly
N
e
-2-[2-(2-methoxyethoxy)ethoxy] acetyl-
L
-lysine-
b
-poly(
L
-leucine) amphi-
philic copolymers by Deming and coworkers [
237
]. For these polymersomes,
the size and structure are dictated primarily by the ordered conformations of
the polymer blocks, in a manner similar to viral capsid assembly. Owing to the
rigid ordered structure of the hydrophobic membrane, the polymersomes showed
great stability and no release of entrapped molecules over a few weeks. Kimura
et al. have also developed fully polypeptide-based but non-naturally-occurring
polymersomes (“peptosomes”) of polysarcosine-
b
-poly(
g
-methyl
L
-glutamate)
synthesized by a NCA polymerization method (Fig.
12a
)[
238
]. The peptosomes
were found to possess stable hydrophobic membrane composed of poly(
g
-methyl
L
-glutamate) chains having
a
-helical structure. Hence, they utilized the peptosomes
as nanocarriers for in vivo imaging probes. The peptosomes labeled with a near-
infrared fluorescence (NIRF) probe showed a relatively long half-life time in the rat
blood stream, which was comparable to that of PEGylated liposomes. Moreover,
NIRF imaging of a small murine cancer was performed using the peptosome as a
nanocarrier (Fig.
12b
,c)[
239
].
In addition to ordered chain conformations, polypeptides contain the abundant
chemical functionality of amino acids. Deming and coworkers have developed fully
naturally occurring polypeptide-based polymersomes composed of polyarginine
(PArg) and polyleucine (PLeu) as a hydrophilic block and hydrophobic block,
respectively [
214
]. The polymersomes are quite stable in physiological conditions
and can encapsulate water-soluble molecules. The remarkable feature of this
material is that the PArg block directs self-assembly for the polymersome forma-
tion and simultaneously provides functionality for efficient intracellular delivery to
the polymersomes. This unique synergy between nanoscale self-assembly and
