Biomedical Engineering Reference
In-Depth Information
Table 1 Polycations with peptide backbone
Polymer
Chemical structure
Poly(L-lysine) (PLL)
O
N
n
H 2 N
Polyaspartamide derivative bearing
1,2-diaminoethane side chains [PAsp(DET)]
O
N
N
x
y
O
O
n
O
HN
HN
NH
NH
H 2 N
H 2 N
onto PLL for targeting specific cells. Although some encouraging results were
obtained in early studies, the rather low transfection efficiency has limited the clini-
cal applications of PLL-based polyplexes, which is ascribed to the poor escape
from the endocytic pathway.
The safety issue is another factor that affects in vivo applications of PLL in gene
therapy. PLL has been found to be not inert, and it may influence many cellular
processes such as the activation of phospholipases and microtubule-associated
protein two kinase (Shier et al. 1984 ; Kyriakis and Avruch 1990 ), membrane stability
and permeability (Kornguth and Stahmann 1961 ; Elferink 1985 ) as well cell divi-
sion (Kundahl et al. 1981 ). In addition, some studies have shown the immunogenicity
of PLL, in a molecular weight dependent manner (Plank et al. 1996 ).
3.1.2
PLL Derivatives
To develop PLL-based gene carriers with enhanced transfection efficacy as well as
lower toxicity, variety of modifications have been performed (Liu et al. 2010 )
(Table 2 ). For example, palmitic acid conjugated PLL (PLL-PA) was employed for
 
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