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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

Flow cytometry images (A) of A549 cells incubated with DOX loaded DOX-hyd-PEG-ALN micelle and DOX loaded DOX-hyd-PEG micelle for 5 min, 30 min and 3 h at 37 °C. Quantitative analysis of flow cytometry images (B), *P < 0.05 vs DOX loaded DOX-hyd-PEG micelle at the same time point; #P < 0.05 vs 30 min of the same micelle. DOX concentration was 10 μg/mL.
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f8: Flow cytometry images (A) of A549 cells incubated with DOX loaded DOX-hyd-PEG-ALN micelle and DOX loaded DOX-hyd-PEG micelle for 5 min, 30 min and 3 h at 37 °C. Quantitative analysis of flow cytometry images (B), *P < 0.05 vs DOX loaded DOX-hyd-PEG micelle at the same time point; #P < 0.05 vs 30 min of the same micelle. DOX concentration was 10 μg/mL.

Mentions: The cellular uptake of DOX loaded DOX-hyd-PEG-ALN micelle and DOX loaded DOX-hyd-PEG micelle by A549 cells were further evaluated by flow cytometry. The results are showed in Fig. 8A,B. The fluorescence intensity augmented with the increase of incubation time. The cellular uptakes of DOX loaded DOX-hyd-PEG-ALN micelle was greater than that of DOX loaded DOX-hyd-PEG micelle on A549 cells. The TEM results showed that both of DOX loaded DOX-hyd-PEG-ALN micelle and DOX loaded DOX-hyd-PEG micelle were generally spherical in shape. Thus, the high intracellular uptake efficiency of DOX loaded DOX-hyd-PEG-ALN micelle was attributed to its small size. Particle size is regarded as a key factor in the cellular uptake of polymeric particles. The cellular uptake and permeability increase with the decrease of particle size5960. For example, Langston Suen WL et al. reported that the cellular uptake of 50 nm nanoparticle was faster than that of 250 nm particle61.


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)

Flow cytometry images (A) of A549 cells incubated with DOX loaded DOX-hyd-PEG-ALN micelle and DOX loaded DOX-hyd-PEG micelle for 5 min, 30 min and 3 h at 37 °C. Quantitative analysis of flow cytometry images (B), *P < 0.05 vs DOX loaded DOX-hyd-PEG micelle at the same time point; #P < 0.05 vs 30 min of the same micelle. DOX concentration was 10 μg/mL.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f8: Flow cytometry images (A) of A549 cells incubated with DOX loaded DOX-hyd-PEG-ALN micelle and DOX loaded DOX-hyd-PEG micelle for 5 min, 30 min and 3 h at 37 °C. Quantitative analysis of flow cytometry images (B), *P < 0.05 vs DOX loaded DOX-hyd-PEG micelle at the same time point; #P < 0.05 vs 30 min of the same micelle. DOX concentration was 10 μg/mL.
Mentions: The cellular uptake of DOX loaded DOX-hyd-PEG-ALN micelle and DOX loaded DOX-hyd-PEG micelle by A549 cells were further evaluated by flow cytometry. The results are showed in Fig. 8A,B. The fluorescence intensity augmented with the increase of incubation time. The cellular uptakes of DOX loaded DOX-hyd-PEG-ALN micelle was greater than that of DOX loaded DOX-hyd-PEG micelle on A549 cells. The TEM results showed that both of DOX loaded DOX-hyd-PEG-ALN micelle and DOX loaded DOX-hyd-PEG micelle were generally spherical in shape. Thus, the high intracellular uptake efficiency of DOX loaded DOX-hyd-PEG-ALN micelle was attributed to its small size. Particle size is regarded as a key factor in the cellular uptake of polymeric particles. The cellular uptake and permeability increase with the decrease of particle size5960. For example, Langston Suen WL et al. reported that the cellular uptake of 50 nm nanoparticle was faster than that of 250 nm particle61.

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