4.5 Article

Arginine-Glycine-Aspartic Acid-Modified Lipid-Polymer Hybrid Nanoparticles for Docetaxel Delivery in Glioblastoma Multiforme

Journal

JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 11, Issue 3, Pages 382-391

Publisher

AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2015.1965

Keywords

Lipid-Polymer Hybrid Nanoparticles; Arginine-Glycine-Aspartic Acid Peptide; Glioblastoma Multiforme; Docetaxel

Funding

  1. National Natural Science Foundation of China [81072599]
  2. National Basic Research Program of China (973 Program) [2013CB932504]

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Hybrid nanoparticles consisting of lipids and the biodegradable polymer, poly (D, L-lactide-co-glycolide) (PLGA), were developed for the targeted delivery of the anticancer drug, docetaxel. Transmission electron microscopic observations confirmed the presence of a lipid coating over the polymeric core. Using coumarin-6 as a fluorescent probe, the uptake efficacy of RGD conjugated lipid coated nanoparticles (RGD-L-P) by C6 cells was increased significantly, compared with that of lipid-polymer hybrid nanoparticles (L-P; 2.5-fold higher) or PLGA-nanoparticles (PLGA-P; 1.76-fold higher). The superior tumor spheroid penetration of RGD-L-P indicated that RGD-L-P could target effectively and specifically to C6 cells overexpressing integrin alpha(v)beta(3). The anti-proliferative activity of docetaxel-loaded RGD-L-P against C6 cells was increased 2.69-and 4.13-fold compared with L-P and PLGA-P, respectively. Regarding biodistribution, the strongest brain-localized fluorescence signals were detected in glioblastomamultiforme (GBM)-bearing rats treated with 1,10-Dioctadecyl-3,3,30,30-tetramethylindotricarb-ocyanine iodide (DiR)-loaded RGD-L-P, compared to rats treated with DiR-loaded L-P or PLGA-P. The median survival time of GBM-bearing rats treated with docetaxel-loaded RGD-L-P was 57 days, a fold increase of 1.43, 1.78, 3.35, and 3.56 compared with animals given L-P (P < 0.05), PLGA-P (P < 0.05), Taxotere (P < 0.01) and saline (P < 0.01), respectively. Collectively, these results support RGD-L-P as a promising drug delivery system for the specific targeting and the treatment of GBM.

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