Biomedical Engineering Reference
In-Depth Information
(a)
120
(b)
120
100
80
60
40
20
100
80
60
40
20
0
0
0
0
1
2
3
4
5
2
4
6
8
DOX conc. (μg
·
mL
-1
)
DOX conc. (μg
·
mL
-1
)
Figure 3.27
Cytotoxicity of DOX-COS-SA and DOX HCl solution toward MCF-7 (a) and MCF-7/Adr (b). For both cells, (
◇
)
DOX-COS-SA-3, (
○
) DOX-COS-SA-6, (
△
) DOX-COS-SA, and (
◆
) DOX HCl solution. Data represent the mean
standard deviation (
n
= 3). (Adapted from Hu, F. Q. et al. 2009.
Biomaterials
30: 1-9.)
and the DOX-COS values of COS-SA in MCF-SA micelles are shown in Figure 3.27. The
IC
50
values for COS-SA in MCF-7a and MCF-7/Adr cells were determined as about 250 μg/
mL, indicating that the present micelles showed low cytotoxicity against cultured cells. It
can be seen that for both MCF-7 and MCF/Adr cells, the IC
50
value of DOX-COS-SA is
related to the DOX content in DOX-COS-SA. The results indicated that the higher the
drug content, the lower the cytotoxicity. For MCF-7/Adr cells, the IC
50
value of DOX HCl
was above 300-fold higher than in sensitive cells. This means that MCF-7/Adr cells were
DOX HCl resistant. Compared to the DOX HCl solution, DOX-COS-SA with different
DOX contents did not show lower cytotoxicity in drug-sensitive MCF-7 cells. However, the
IC
50
value of DOX-COS-SA against MCF-7/Adr cells was only slightly higher than that of
DOX-COS-SA against MCF-7 drug-sensitive cells and was much lower than that of DOX
HCl solution in MCF-7/Adr cells. The results meant that DOX-COS-SA micelles could
reverse the drug resistance of MCF-7/Adr cells. The reversal power of DOX-COS-SA
against MCF-7/Adr cells was about 4-10.
ADR and DOX-CSO-SA-10 treatments effectively suppressed tumor growth; for exam-
ple, 5 days after i.v. injection, tumor volumes of nude mice treated with ADR and DOX-
CSO-SA-10 were significantly smaller than those treated with saline and blank COS-SA
micelle solution (
p
< 0.05); after 10 days,
p
< 0.001. There were no significant differences
between the tumor volumes treated with saline and blank COS-SA (
p
> 0.05). After 10
days, the tumor volumes treated with ADR (total DOX dosage was 7 mg/kg) were signifi-
cantly smaller than those treated with DOX-COS-SA (total DOX dosage was 7 mg/kg),
but were significantly bigger than those treated with DOX-COS-SA-10 (total DOX dosage
was 14 mg/kg) (
p
< 0.05). However, after 20 days, there were no significant differences
(
p
> 0.05). But for the tumor volumes treated with DOX-COS-SA-10 (total DOX dosage
was 7 mg/kg) and DOX-COS-SA-10 (total DOX dosage was 14 mg/kg), there were evi-
dent significant differences (
p
< 0.05). The doses of these five groups were within the safe
range. However, the injection of ADR with 2 mg/kg body weight for 7 days consecutively
led to the death of nude mice (only 1 survived on the 15th day). This means that DOX-
COS-SA was safer than ADR. The tumor inhibition rate of ADR (total DOX dosage was
7 mg/kg; the total drug dose was 64.33 ± 7.01%; DOX-COS-SA-10 with 7 mg/kg was
63.89 ± 7.64%; and DOX-COS-SA-10 with 14 mg/kg total drug dose was 80.70 ± 2.55%. All
the tumor inhibition values were larger than 60%, which was considered to be effective
treatment.
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