Biomedical Engineering Reference
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d n 4 y 3 n g | 3
Figure 4.6
Thermoresponsive PEI derivatives as gene vectors.
vector formulations for gene transfer in vitro and murine lungs in vivo. 51 They
found that in vivo experiments resulted in up to three-fold higher gene
expression in the lung with lactose as lyoprotectant compared to sucrose or
trehalose.
Yang et al. synthesized thermoresponsive diblock copolymers, poly[2-(2-
methoxyethoxy)ethyl methacrylate]-b-poly(2-hydroxyethyl methacrylate), with
low polydispersity by atomic transfer radical polymerization, which were then
grafted with 1200 Da PEI to form PEIMH copolymer vectors (Figure 4.6). 52
The lower critical solution temperature (LCST) of PEIMH was dependent
upon the grafting number of the PEI. When the temperature was elevated
above the LCST, PEIMH could condense DNA more efficiently due to the
shielding effect of collapsed PMEO2MA chains. Meanwhile, the contracted
PMEO2MA chains led to more exposure of surface positive charges of the
PEIMH/pDNA complexes, which was favorable for gene transport. Moreover,
PEIMH
showed
superior
transfection
efficiency
and
considerably
lower
cytotoxicity compared to 25 kDa PEI.
4.3 Chitosan-Based Gene Vectors
Natural cationic polymers, such as chitosan, which are biocompatible,
biodegradable, and have low toxicity, have been widely used as alternative
gene vectors and much attention has been paid to them. Chitosan is composed
of D -glucosamine and N-acetyl- D -glucosamine linked by b-(1,4)-glycosidic
linkages. The above positive characteristics as well as multiple functionaliza-
tion make chitosan a good gene carrier candidate and a series of experiments
confirmed that chitosan could effectively combine with pDNA and protect it
from nuclease degradation. In addition, the amino group of chitosan could
bind with the negatively charged cell-membrane surface by electrostatic
attraction and hydrogen bonding, which could increase the cell uptake of
pDNA. However, the application of chitosan is significantly limited by its poor
solubility (the amino groups on chitosan are only partially protonated at a
 
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