Biomedical Engineering Reference
In-Depth Information
with polycations is a common approach for intracellular delivery; this includes
PEGylated polycations,
21
polyethylenimine (PEI) complexes,
22,23
cationic block
copolymers,
24
and dendrimers.
25-27
However, the large size and/or considerable
toxicity
28,29
of cationic lipid particles and cationic polymers may cause problems
for in vivo utilization.
Some members of a family of natural polysaccharides, called b-1,3-glucans,
are approved for clinical use in Japan and have been used for the treatment of
uterine cancer.
30
It has been demonstrated that b-1,3-glucans can form novel
complexes with homo-oligodeoxynucleotides (homo-ODNs) via a combination
of hydrogen bonding and hydrophobic interactions (Figure 8.1).
31-33
The
complexation is accomplished in a rather peculiar manner. Thus the b-1,3-
glucans adopt a triple helix in neutral water and the helix dissociates into single
chains in dimethyl sulfoxide or alkaline solution (.0.25 N NaOH
aq
).
34
When
the solvent of the single chains is substituted with neutral water, the original
triple helix is regenerated.
35
When a particular polynucleotide such as poly(C)
or poly(dA) is present in this process, two main-chain glucoses of b-1,3-glucans
and one ODN base form a stoichiometric complex instead of retrieving the
original triple helix. The complexation not only provides scientifically
interesting issues but also a new tool to deliver biologically functional
polynucleotides to specific targets. Among the b-1,3-glucans, we have focused
on schizophyllan (SPG; Figure 8.1), because SPG in a medically approved
grade
d
n
4
y
3
n
g
|
0
is
available
in
Japan
and
its
molecular
characteristics
are
well
understood.
30
The fungi containing b-1,3-glucans have been used in Chinese herbal
medicine for a long time
36
and, among others, SPG and lentinan
37
have been
commercially distributed as medicines for various cancers and health foods for
Figure 8.1
Repeating unit of schizophyllan (SPG) and poly(deoxyadenylic acid)
(dA
x
) and an illustration of their complexation and stoichiometric
structures of the triple helix of SPG and the complex, denoted tSPG and
dA
x
/SPG.
