Biomedical Engineering Reference
In-Depth Information
their hierarchy architecture and facile modification owing to their numerous
terminal groups.
6
5.4.2 Application as Gene Vectors
The nonviral gene vectors can be categorized into three kinds: cationic lipids,
peptides, and cationic polymers. The method of liposome-mediated gene
transfer is one of the earliest strategies used to introduce exogenous genetic
material into cancer cells. The headgroup of the lipid can be adjusted to
cationic states, thus increasing the cellular uptake. As the second vector,
peptide oligonucleotide conjugates offer a unique strategy of delivering genes
into cells with high efficiency and cell specificity. To deliver oligonucleotides
into cells, these peptide vectors rely on short sequences of basic amino acid
residues which readily penetrate the plasma membrane.
71
Although the
development of liposomes and peptides persists, researchers have given more
attention to the exceptional gene vehicles of cationic polymers and their
dendritic derivatives.
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The typical polymeric materials include poly(
L
-lysine)
(PLL), polyethylenimine (PEI), polymethacrylate (e.g. PDMAEMA), car-
bohydrate-based polymers, and poly(amido-amine) (PAMAM). Most of these
structures comprise amine groups, which is conducive to compacting DNA
and penetrating the cell membrane. By introduction of a dendritic structure
into the polymer backbone, the cationic polymers exhibit compact and
globular structures in combination with a great number of various amine
groups, which facilitates DNA condensation, gene delivery, and transfection
improvement. Our group has developed several methods to prepare nonviral
gene vectors.
12,23,62,73-75
Recently, Dong et al. developed a facile supramole-
cular approach for the preparation of charge-tunable dendritic polycations via
the host-guest interaction between two different cationic b-CD derivative
hosts and an adamantane-modified hyperbranched polyglycerol (HPG-AD)
guest as gene vectors.
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The multifunctionality was given to the dendritic
polymers by the dynamic-tunable ability of supramolecular polymers via
noncovalent interactions, thus making the optimization of structural
parameters much easier than that of covalent polymerizations or modifica-
tions. For example, the parameters of charge density and charge distribution
on the surface of vectors can be modulated, which fully embodies the
advantages of HBPs and supramolecular chemistry in gene transfection. The
functional HBPs provide a potential strategy to promote cationic polymers as
safe
d
n
4
y
3
n
g
|
1
and
efficient
nonviral
gene
carriers
with
satisfied
gene
delivery
performance.
5.5 Summary
A series of synthetic strategies for HBPs have been developed, such as SCVP
and SCROP, and meanwhile other novel preparation methodologies are
continuously being proposed. Subsequently, additional functions enhance the
