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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

The schematic illustration of construction of DOX-loaded DOX-hyd-PEG-ALN micelle and pH triggered intracellular drug release.This figure was drawn by Wei-liang Ye. The mouse picture was taken by Wei-liang Ye during the animal experiment.
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f1: The schematic illustration of construction of DOX-loaded DOX-hyd-PEG-ALN micelle and pH triggered intracellular drug release.This figure was drawn by Wei-liang Ye. The mouse picture was taken by Wei-liang Ye during the animal experiment.

Mentions: In this paper, in order to increase the therapeutic effect of DOX on bone metastases, doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) copolymer was synthesized. The hydrophilic and hydrophobic segment was conjugated by the hydrazone bond which was responsive to the acidic microenvironment of endolysosome in tumor cell24. Then the copolymer self-assembled into micelle. The free DOX was encapsulated into the micelle (Fig. 1). The binding affinity of the DOX-hyd-PEG-ALN micelle with HA was evaluated. In addition, the pH sensitivity as well as drug release properties of DOX-hyd-PEG-ALN micelle was investigated. Finally, the in vitro cytotoxicity and in vivo anti-tumor activity of DOX loaded DOX-hyd-PEG-ALN micelle were further studied.


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)

The schematic illustration of construction of DOX-loaded DOX-hyd-PEG-ALN micelle and pH triggered intracellular drug release.This figure was drawn by Wei-liang Ye. The mouse picture was taken by Wei-liang Ye during the animal experiment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: The schematic illustration of construction of DOX-loaded DOX-hyd-PEG-ALN micelle and pH triggered intracellular drug release.This figure was drawn by Wei-liang Ye. The mouse picture was taken by Wei-liang Ye during the animal experiment.
Mentions: In this paper, in order to increase the therapeutic effect of DOX on bone metastases, doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) copolymer was synthesized. The hydrophilic and hydrophobic segment was conjugated by the hydrazone bond which was responsive to the acidic microenvironment of endolysosome in tumor cell24. Then the copolymer self-assembled into micelle. The free DOX was encapsulated into the micelle (Fig. 1). The binding affinity of the DOX-hyd-PEG-ALN micelle with HA was evaluated. In addition, the pH sensitivity as well as drug release properties of DOX-hyd-PEG-ALN micelle was investigated. Finally, the in vitro cytotoxicity and in vivo anti-tumor activity of DOX loaded DOX-hyd-PEG-ALN micelle were further studied.

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