Biomedical Engineering Reference
In-Depth Information
A typical instance is the interlayer-crosslinked polypeptide nanogel that
has been developed in Shuai's group [78]. As shown in Figure 15.6A, the
pH and reduction dual-responsive nanogel based on poly(ethylene gly-
col)-
block
-poly(
N
-(2-mercaptoethyl) L-aspartamide)-
block
-poly(
N
-(2-
(diisopropylamino)ethyl) L-aspartamide)) (PEG-
b
-PMELA-
b
-PDIPLA)
was prepared through the disuli de-crosslinking of PMELA interlayer at
pH 10.0. h e nanogel showed pH and reduction dual-responsive properties
(
a
)
(
b
)
A
B
pH10
H
2
O
pH5.0
DTT
(
c
)
pH7.4
pH10
ICM
(47.7 nm)
HP-ICM
(59.4 nm)
(
a
)
D
High
PEG-
b
-PMELA-
b
-PDIPLA
DOX
C
Nuclei
DOX
Merged
Bright Field
low
(
b
)
HP-ICM
1200
1000
800
600
400
200
50
40
30
20
10
0
PEG-PCL micelle
Free DOX
PBS
Administration
0
5
10
15
20
25
30
Time/d
Figure 15.6
(A) Formation and structural transitions of the dual-responsive nanogel
(
n
= 45,
m
= 15 and
k
= 14; determined by
1
H NMR). (B) TEM microimages of the
nanoassemblies at (a) pH 7.4, (b) 5.0, (c) 7.4 with 10.0 mM DTT and (d) 5.0 with
10.0 mM DTT. h e nanogel shown in (a) was decorated with Au, and other samples
were stained with uranyl acetate. (C) Intracellular DOX release and migration into nuclei
observed by CLSM. Nuclei were stained with Hoechst 33342 (blue). (D) (a)
In vivo
DOX
l uorescence images showing passive tumor accumulation of the DOX-loaded nanogel
at er tail-vein injection into nude mice bearing the Bel-7402 xenograt (dose: 5.0 mg DOX
per kg body weight); (b) Tumor growth inhibition in nude mice bearing the Bel-7402
tumor at er tail-vein injection of dif erent formulations (
n
= 20; dose: equivalent 5.0 mg
DOX per kg body weight per injection for DOX or the DOX-loaded nanoparticles).
*
p
< 0.01 versus PEG-
b
-PCL micelle. Reproduced with permission from [78].
