Biomedical Engineering Reference
In-Depth Information
exhibited lower cytotoxicity and higher transfection efficiency in HepG2 cells
compared to 25 kDa PEI. Moreover, these HA-modified complexes were
obviously accumulated in tumor after i.v. administration, which indicated that
HA could assist PEI targeting to the tumor.
One of the best-characterized targeting ligands for tumor treatment is folate,
since folate receptors (FRs) exhibit limited expression on healthy cells, but are
overexpressed in certain cancer cells. Folate-modified PEI has previously been
shown to promote target-specific gene delivery both in vitro and in vivo,
showing superior performance compared to PEI. Liang et al. found that when
folate-PEG-PEI was used for the delivery of therapeutic genes, by direct
injection into tumors of glioma-xenografted rats, a significant antitumor effect
was achieved.
35
Zhang et al. synthesized folate/PEG-modified PEI as a delivery
system for tumor targeting transfer of mcDNA.
36
These folate-labeled
polyplexes containing mcDNA exhibited strong tumor targeting capability
and high levels of gene expression both in vitro and in vivo.
Efforts have been made in order to attain neuron-specific complexes.
Oliveira et al. developed a PEI-based multi-component gene vector targeted to
peripheral nervous system cells.
37
A thiolated PEI/DNA complex was used as
the complex core, and a PEG-modified tetanus toxin fragment was grafted
onto the core as the targeting moiety. The results demonstrated that these
ternary vectors were able to transfect primary cultures of dorsal root ganglion
dissociated neurons in a targeted manner and elicit the expression of a relevant
neurotrophic factor. Hwang et al. synthesized rabies virus glycoprotein
(RVG)-labeled SS-PEI as neuron-specific miR-124a delivery to neuron in
vivo.
38
This compound showed low toxicity and high transfection efficiency in
acetylcholine receptor-positive Neuro2a cells.
Gene therapy is a promising method for osteoarthritis and cartilage injury.
However, specifically delivering target genes into chondrocytes is a great
challenge because of their non-vascularity and the dense extracellular matrix of
cartilage. Pi et al. constructed a cartilage-targeting gene delivery system by
conjugating chondrocyte-homing peptide to PEI.
39
This system showed
apparently cartilage-targeting property in an in vivo assay, so could be used
as a specific cartilage-targeting vector for cartilage disorders.
To improve the gene delivery efficiency and safety of nonviral vectors in liver
cells, Zeng et al. synthesized a series of biotinylated PEI/avidin bioconjugates
that presented less toxic and higher gene expression in HepG2 cells due to the
biocompatibility of avidin and the specific interactions between avidin and
HepG2 cells.
40,41
They also confirmed the optimum conditions for in vitro gene
transfection of these bioconjugates in HepG2 cells.
42
Tumor cells with a high
rate of proliferation usually overexpress transferrin receptors, so they could act
as ideal targets in antitumor gene delivery. Recently, this group developed a
biotinylated transferrin/avidin/biotinylated disulfide-containing PEI bioconju-
gate (TABP-SS) mediated p53 gene delivery system attributed to a ''avidin-
biotin bridge''.
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TABP-SS exhibited much lower cytotoxicity and higher
