Biomedical Engineering Reference
In-Depth Information
alternative method to construct a nonviral delivery system for targeted gene
transfer into breast cancer cells.
4.5.4 Asp-Based Peptides
Kataoka's group found that polyplex micelles formed with plasmid DNA and
PEG-b-poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)]
exhibit effective endosomal escaping properties based on di-protonation of
diamine side chains with decreasing pH, which improves their transfection
efficiency and thus are promising candidates for local in vivo gene transfer. 99
Recently, they improved the design of PEG-PAsp(DET)-based gene vectors by
incorporating a cholesterol moiety into the terminus of the PAsp(DET)
segment in the block copolymer. 100 PEG-PAsp(DET)-Chole micelles could
be formed over the stoichiometric charge ratio due to self-association
of cholesterol, and increased transfection efficiency at low N/P ratios.
Furthermore, cholesterol introduction led to increased stability of polyplex
micelles in the blood, which resulted in significant suppression of subcutaneous
pancreatic tumor growth by intravenous injection of polyplex micelles loading
sFlt-1 pDNA. They also succeeded in bone regeneration by introducing
osteogenic factor-expressing genes for bone defects in the mouse skull. 101
Recently, the same group improved the safety and transfection efficiency of
this polyplex micelle system by adding an anionic polycarbohydrate,
chondroitin sulfate (CS). 102 The results showed that the addition of CS
markedly reduced tissue damage and subsequent inflammatory responses in
the skeletal muscle and lungs of mice following in vivo gene delivery with the
polyplex micelles, which led to prolonged transgene expression in the target
organs. This combination of polyplex micelles and CS holds great promise for
safe and efficient gene introduction in clinical settings.
Lai et al. synthesized pluronic P85-based cationomers comprising poly{N-
[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (P[Asp(DET)]) cationic copoly-
mers for transfection (Scheme 4.12). 103 They demonstrated that substituting
the hydrophilic PEG shell with an amphiphilic pluronic P85 layer on the
surface of the polyplex could lead to higher transfection efficiency of the
P[Asp(DET)]-based pDNA delivery system. The amphiphilic nature of the P85
shell promoted cellular uptake of the polyplex particles and subsequently
increased the transfection ability of the particles.
d n 4 y 3 n g | 3
4.6
Other Gene Vectors
4.6.1 Lipid-Based Vectors
For gene carriers, cationic liposomes have recently emerged as leading nonviral
vectors in worldwide gene therapy clinical trials. However, cytotoxic effects or
apoptosis are often observed, which is mostly dependent on the cationic lipid
used. In order to reduce the cytotoxicity, Li et al. synthesized a new cationic
 
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