Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles

  • Authors:
    • Ai‑Jun Li
    • Yue‑Hua Zheng
    • Guo‑Dong Liu
    • Wei‑Sheng Liu
    • Pei‑Cheng Cao
    • Zhen‑Fu Bu
  • View Affiliations

  • Published online on: November 28, 2014     https://doi.org/10.3892/mmr.2014.3017
  • Pages: 3078-3086
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the blood‑brain‑tumor barrier. In the present study, cyclic Arginine‑Glycine‑Aspartic acid‑D‑Tyrosine‑Lysine [c(RGDyK)], that has a high binding affinity to integrin αvβ3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acid‑polyethylene glycol (DTX‑PLA‑PEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the Arginine‑Glycine‑Aspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTX‑PLA‑PEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas non‑targeted micelles showed limited transport ability. Furthermore, RGD‑linked micelles showed marked anti‑glioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligand‑mediated drug delivery may improve the efficacy of brain cancer chemotherapy.
View Figures
View References

Related Articles

Journal Cover

April-2015
Volume 11 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Li AJ, Zheng YH, Liu GD, Liu WS, Cao PC and Bu ZF: Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles. Mol Med Rep 11: 3078-3086, 2015.
APA
Li, A., Zheng, Y., Liu, G., Liu, W., Cao, P., & Bu, Z. (2015). Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles. Molecular Medicine Reports, 11, 3078-3086. https://doi.org/10.3892/mmr.2014.3017
MLA
Li, A., Zheng, Y., Liu, G., Liu, W., Cao, P., Bu, Z."Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles". Molecular Medicine Reports 11.4 (2015): 3078-3086.
Chicago
Li, A., Zheng, Y., Liu, G., Liu, W., Cao, P., Bu, Z."Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles". Molecular Medicine Reports 11, no. 4 (2015): 3078-3086. https://doi.org/10.3892/mmr.2014.3017