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PEGylated Poly(amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors.

Abstract
A dual-targeting drug carrier (PAMAM-PEG-WGA-Tf) based on the PEGylated fourth generation (G = 4.0) PAMAM dendrimer with transferrin (Tf) and wheat germ agglutinin (WGA) on the periphery and doxorubicin (DOX) loaded in the interior was synthesized and its BBB penetration and tumor targeting properties were explored. DLS and TEM measurements revealed the size of PAMAM-PEG-WGA-Tf was in the range of 14-20 nm. It reduced the cytotoxicity of DOX to the normal cells greatly, while efficiently inhibited the growth rate of the C6 glioma cells. The assay of transport across the BBB showed that PAMAM-PEG-WGA-Tf delivered 13.5% of DOX in a period of 2 h, demonstrating an enhanced transport ratio as compared to the ratio of 8% for PAMAM-PEG-WGA, 7% for PAMAM-PEG-Tf and 5% for free DOX in the same period of time. The accumulation of DOX in the tumor site was increased due to the targeting effects of both Tf and WGA, leading to the complete breakage of the avascular C6 glioma spheroids in vitro.
AuthorsHai He, Yan Li, Xin-Ru Jia, Ju Du, Xue Ying, Wan-Liang Lu, Jin-Ning Lou, Yan Wei
JournalBiomaterials (Biomaterials) Vol. 32 Issue 2 Pg. 478-87 (Jan 2011) ISSN: 1878-5905 [Electronic] Netherlands
PMID20934215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Antibiotics, Antineoplastic
  • Dendrimers
  • Drug Carriers
  • PEG-PAMAM
  • Transferrin
  • Polyethylene Glycols
  • Doxorubicin
Topics
  • Animals
  • Antibiotics, Antineoplastic (administration & dosage, therapeutic use)
  • Blood-Brain Barrier (metabolism)
  • Brain Neoplasms (drug therapy)
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Dendrimers (chemistry)
  • Doxorubicin (administration & dosage, therapeutic use)
  • Drug Carriers (chemistry)
  • Glioma (drug therapy)
  • Mice
  • Polyethylene Glycols (chemistry)
  • Transferrin (administration & dosage, therapeutic use)

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