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Doxorubicin-poly (ethylene glycol)-alendronate self-assembled micelles for targeted therapy of bone metastatic cancer.

Ye WL, Zhao YP, Li HQ, Na R, Li F, Mei QB, Zhao MG, Zhou SY - Sci Rep (2015)

Bottom Line: In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS.Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX.In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.

ABSTRACT
In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

No MeSH data available.


Related in: MedlinePlus

Fluorescence microscope images (A) of A549 cells incubated with DOX loaded DOX-hyd-PEG-ALN micelle for 5 min, 30 min and 3 h at 37 °C. Quantitative analysis of fluorescence microscope images (B), *P < 0.05 vs cytoplasma at the same time point. DOX concentration was 10 μg/mL. The pink region shows the localization of DOX (red) in the nucleus (blue).
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f7: Fluorescence microscope images (A) of A549 cells incubated with DOX loaded DOX-hyd-PEG-ALN micelle for 5 min, 30 min and 3 h at 37 °C. Quantitative analysis of fluorescence microscope images (B), *P < 0.05 vs cytoplasma at the same time point. DOX concentration was 10 μg/mL. The pink region shows the localization of DOX (red) in the nucleus (blue).

Mentions: In this experiment, DOX itself was used as a fluorescence marker57. As showed in Fig. 7A,B, there was little red DOX fluorescence in the cytoplasm and nucleus of the A549 cells when the cells were incubated with the DOX loaded DOX-hyd-PEG-ALN micelle for 5 min. The intracellular DOX fluorescence intensity gradually increased when the incubation time increased from 5 min to 30 min. After A549 cells were incubated with DOX loaded DOX-hyd-PEG-ALN micelle for 30 min, red DOX fluorescence intensity in the cytoplasm was the same as in the nucleus. After the A549 cells were incubated with DOX loaded DOX-hyd-PEG-ALN micelle for 3 h, the DOX red fluorescence almost localized completely in the nucleus of the A549 cells. This result indicated that DOX loaded DOX-hyd-PEG-ALN micelle was taken up efficiently by A549 cells, and DOX was released from DOX loaded DOX-hyd-PEG-ALN micelle and trafficked to the nucleus of A549 cell58.


Doxorubicin-poly (ethylene glycol)-alendronate self-assembled micelles for targeted therapy of bone metastatic cancer.

Ye WL, Zhao YP, Li HQ, Na R, Li F, Mei QB, Zhao MG, Zhou SY - Sci Rep (2015)

Fluorescence microscope images (A) of A549 cells incubated with DOX loaded DOX-hyd-PEG-ALN micelle for 5 min, 30 min and 3 h at 37 °C. Quantitative analysis of fluorescence microscope images (B), *P < 0.05 vs cytoplasma at the same time point. DOX concentration was 10 μg/mL. The pink region shows the localization of DOX (red) in the nucleus (blue).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588583&req=5

f7: Fluorescence microscope images (A) of A549 cells incubated with DOX loaded DOX-hyd-PEG-ALN micelle for 5 min, 30 min and 3 h at 37 °C. Quantitative analysis of fluorescence microscope images (B), *P < 0.05 vs cytoplasma at the same time point. DOX concentration was 10 μg/mL. The pink region shows the localization of DOX (red) in the nucleus (blue).
Mentions: In this experiment, DOX itself was used as a fluorescence marker57. As showed in Fig. 7A,B, there was little red DOX fluorescence in the cytoplasm and nucleus of the A549 cells when the cells were incubated with the DOX loaded DOX-hyd-PEG-ALN micelle for 5 min. The intracellular DOX fluorescence intensity gradually increased when the incubation time increased from 5 min to 30 min. After A549 cells were incubated with DOX loaded DOX-hyd-PEG-ALN micelle for 30 min, red DOX fluorescence intensity in the cytoplasm was the same as in the nucleus. After the A549 cells were incubated with DOX loaded DOX-hyd-PEG-ALN micelle for 3 h, the DOX red fluorescence almost localized completely in the nucleus of the A549 cells. This result indicated that DOX loaded DOX-hyd-PEG-ALN micelle was taken up efficiently by A549 cells, and DOX was released from DOX loaded DOX-hyd-PEG-ALN micelle and trafficked to the nucleus of A549 cell58.

Bottom Line: In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS.Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX.In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.

ABSTRACT
In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

No MeSH data available.


Related in: MedlinePlus