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Fig. 3 Cytotoxicity of the prodrugs and prodrug/drug complexes in HeLa
45 cells (a), Ht-29 cells (b) and Cos7 cells (c) after 48h of incubation. (d)
The IC50 values of the prodrugs and prodrug/drug complexes in different
cell lines.
Fig. 2 The CLSM images of HeLa cells (A), (B) and Cos7 cells (C). (A),
(C) were incubated with BPD/Fluorescein and (B) was incubated with
mPD/Fluorescein for 1 h. 1, 2, 3 and 4 indicated the Hochest 33258,
5 Fluorescein, Dox and merged channels, respectively (Dox: 50 μg/mL and
Fluorescein: 12 μg/mL). The scale bar is 20 μm.
loading capacity and therapeutic efficiency. We hope this strategy
50 will be utilized to facilitate delivering multi-therapeutic agents for
a variety of purposes especially overcoming multi-drug resistance.
However, limited by the rate of hydrolysis, the formulation of
prodrug/drug complexes exhibited superior therapeutic efficacy
than single prodrug. The optimal formulation was BPD/CPT
10 complexes and the IC50 value (0.74 μg/mL) was about one tenth
of the IC50 value of the BPD/Dox complexes. It indicated that the
combination delivery of dual drugs indeed improved the therapy
efficacy as compared to the single drug formulation.
This work was financially supported by National Basic Research
Program of China (2011CB606202 and 2009CB930300).
Similar results (IC50 mPD> IC50 BPD> IC50 BPD/Dox > IC50
)
55 Notes and references
BPD/CPT
15 could be found in Ht-29 cells and Cos7 cells (Table S1). It was
noted that both prodrug and prodrug/drug complexes showed
more cytotoxicity in cancerous cells than non-cancerous cell. For
example, the IC50 value of BPD/CPT (the optimal formulation) in
Cos7 cells was equivalent to 2.8 times of the value in HeLa and
20 about 3.5 times in Ht-29 cells. This contrast was even more
strongly as taking into account of the cytotoxicity of free Dox and
free CPT. The IC50 values of free Dox in three kinds of cell lines
were 0.72 μg/mL, 0.32 μg/mL and 0.18 μg/mL, respectively; the
IC50 values of free CPT in these cell lines were 0.33 μg/mL, 0.07
25 μg/mL and 0.02 μg/mL, respectively (in the order of HeLa, Ht-29
and Cos7). It indicated that free Dox and CPT showed severe side
toxic effect in non-cancerous cell. Therefore, BPD/CPT complex
showed comparable therapy efficacy of free drugs in cancerous
cells and effectively restrained the side effect of drugs in non-
30 cancerous cells. The prodrug/drug complexes have a great
potential for cancer therapy.
Polymers of Ministry of EducationCollege of Chemistry and Molecular
Science,Wuhan University, Wuhan, 430072, P. R. China;E-mail:
60 † Electronic Supplementary Information (ESI) available: [Synthesis,
characterization, andother experimental details can be found in theESI].
See DOI: 10.1039/b000000x/
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Conclusions
In summary, we demonstrated here a new type of DDS based on
the prodrug/drug complexes without any inert materials. The
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