Biomedical Engineering Reference
In-Depth Information
DNA.
141
They further increased the plasmid DNA and phosphorothioate 29-
OMe oliogonucleotides (ps-MeON) transfection efficiency and minimized the
cytotoxicity of cSCKs by introducing tertiary amines into the shell by chemical
modification of the precursor block copolymer.
142
The reversible addition-fragmentation chain transfer (RAFT) polymeriza-
tion technique allows successful and facile synthesis of cationic glycopolymers
containing pendant sugar moieties in the absence of protecting group
chemistry. Ahmed et al. synthesized well-defined cationic glycopolymers of
varying molecular weight, cationic chain length, carbohydrate to cationic
content ratio, and different architecture (block versus random polymers) by
RAFT polymerization.
143
It was found that the copolymer architecture largely
affected the toxicity, DNA condensation ability, and gene delivery efficacy.
These statistical copolymers of 3-aminopropyl methacrylamide (APMA) or 2-
aminoethyl methacrylamide (AEMA) and 3-gluconamidopropyl methacryla-
mide (GAPMA) showed lower toxicity and higher gene expression in the
presence
d
n
4
y
3
n
g
|
3
and
absence
of
serum,
compared
to
the
corresponding
diblock
copolymers.
Ma et al. synthesized poly(aminoethyl methacrylate) (PAEMA), poly(3-
amino-2-hydroxypropyl methacrylate) (PAHPMA), poly[2-(2-aminoethylami-
no)ethyl methacrylate] (PAEAEMA) and poly[3-(2-aminoethylamino)-2-
hydroxypropyl methacrylate] (PAEAHPMA) using atom transfer radical
polymerization.
144
The results indicated that hydroxyl groups might increase
the binding capacity to DNA and decrease the surface charge of the polymer/
DNA complexes due to the formation of hydrogen bonds between the
polymers and DNA. This effect of hydroxyl groups decreased with increasing
amino group density on the polymer.
There has been success in applying a semi-rational approach to nonviral
gene delivery vector development using a combinatorial/parallel synthesis
approach to construct libraries of materials with unique molecular structures.
Gabrielson et al. have described a library approach to gene delivery vector
development that relies on the supramolecular self-assembly of individual
components instead of chemical reactions.
145
Each component in the described
system is capable of performing a single and well-defined purpose: DNA
binding (dioleylspermine), membrane permeation (oligoarginine), or targeting
(folic acid). A combination of electrostatic attraction and the hydrophobic
effect is used to bring the individual groups together to form nanoscale
complexes with DNA. Because the components responsible for DNA binding,
membrane permeation, and targeting are separate, it is possible to alter the
balance between hydrophilic and hydrophobic groups by varying the relative
amounts in the final formulation. They could readily identify cell-specific
formulations that have greater transfection efficiency than the individual
components and have superior transfection efficiency to Lipofectamine 2000
under similar conditions.
Takemoto et al. reported the synthesis of siRNA-grafted polymers with a
disulfide linkage to improve the physicochemical properties and transfection
