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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

1H NMR spectrum of DOX, ALN, PEG and DOX-hyd-PEG-ALN.
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f3: 1H NMR spectrum of DOX, ALN, PEG and DOX-hyd-PEG-ALN.

Mentions: The 1H NMR spectrum of DOX-hyd-PEG-ALN is showed in Fig. 3. The ALN in DOX-hyd-PEG-ALN was verified by the signals at peak e, f and h (δ = 2.7, 2.3 and 1.4 ppm, respective). Moreover, the DOX in DOX-hyd-PEG-ALN was verified by the signals at peak b, c and d (δ = 5.4, 4.0 and 3.3 ppm, respective)24. The appearance of signal at peak i (δ = 7.8 ppm, −N=NH−) confirmed the hydrazone bond connection between DOX and PEG. The appearance of signal at peak g (δ = 7.6 ppm, −CONH−) confirmed the amide bond connection between ALN and PEG. The PEG backbone in the conjugate was verified by the signal at peak a (δ = 3.6 ppm)14. The IR spectrum of the DOX-hyd-PEG-ALN is showed in Fig. 4. The peak at 3300 ~ 3500 was corresponding to amino bond stretching bands, peak at 1634 was corresponding to the C=C stretching vibration band, peak at 1608 was corresponding to the hydrazone bond stretching vibration band, peaks at 461 and 546 were corresponding to the O−P−O stretching bands, and peak at 1362 was corresponding to the P=O vibration band3637.


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)

1H NMR spectrum of DOX, ALN, PEG and DOX-hyd-PEG-ALN.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: 1H NMR spectrum of DOX, ALN, PEG and DOX-hyd-PEG-ALN.
Mentions: The 1H NMR spectrum of DOX-hyd-PEG-ALN is showed in Fig. 3. The ALN in DOX-hyd-PEG-ALN was verified by the signals at peak e, f and h (δ = 2.7, 2.3 and 1.4 ppm, respective). Moreover, the DOX in DOX-hyd-PEG-ALN was verified by the signals at peak b, c and d (δ = 5.4, 4.0 and 3.3 ppm, respective)24. The appearance of signal at peak i (δ = 7.8 ppm, −N=NH−) confirmed the hydrazone bond connection between DOX and PEG. The appearance of signal at peak g (δ = 7.6 ppm, −CONH−) confirmed the amide bond connection between ALN and PEG. The PEG backbone in the conjugate was verified by the signal at peak a (δ = 3.6 ppm)14. The IR spectrum of the DOX-hyd-PEG-ALN is showed in Fig. 4. The peak at 3300 ~ 3500 was corresponding to amino bond stretching bands, peak at 1634 was corresponding to the C=C stretching vibration band, peak at 1608 was corresponding to the hydrazone bond stretching vibration band, peaks at 461 and 546 were corresponding to the O−P−O stretching bands, and peak at 1362 was corresponding to the P=O vibration band3637.

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