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PEG-PLA nanoparticles modified with APTEDB peptide for enhanced anti-angiogenic and anti-glioma therapy.

Abstract
Tumor neovasculature and tumor cells dual-targeting chemotherapy can not only destroy the tumor neovasculature, cut off the supply of nutrition and starve the tumor cells, but also directly kill tumor cells, holding great potential in overcoming the drawbacks of anti-angiogenic therapy only and improving the anti-glioma efficacy. In the present study, by taking advantage of the specific expression of fibronectin extra domain B (EDB) on both glioma neovasculature endothelial cells and glioma cells, we constructed EDB-targeted peptide APTEDB-modified PEG-PLA nanoparticles (APT-NP) for paclitaxel (PTX) loading to enable tumor neovasculature and tumor cells dual-targeting chemotherapy. PTX-loaded APT-NP showed satisfactory encapsulated efficiency, loading capacity and size distribution. In human umbilical vein endothelial cells, APT-NP exhibited significantly elevated cellular accumulation via energy-dependent, caveolae and lipid raft-involved endocytosis, and improved PTX-induced apoptosis therein. Both in vitro tube formation assay and in vivo matrigel angiogenesis analysis confirmed that APT-NP significantly improved the antiangiogenic ability of PTX. In U87MG cells, APT-NP showed elevated cellular internalization and also enhanced the cytotoxicity of the loaded PTX. Following intravenous administration, as shown by both in vivo live animal imaging and tissue distribution analysis, APT-NP achieved a much higher and specific accumulation within the glioma. As a result, APT-NP-PTX exhibited improved anti-glioma efficacy over unmodified nanoparticles and Taxol(®) in both subcutaneous and intracranial U87MG xenograft models. These findings collectively indicated that APTEDB-modified nanoparticles might serve as a promising nanocarrier for tumor cells and neovasculature dual-targeting chemotherapy and hold great potential in improving the efficacy anti-glioma therapy.
AuthorsGuangzhi Gu, Quanyin Hu, Xingye Feng, Xiaoling Gao, Jiang Menglin, Ting Kang, Di Jiang, Qingxiang Song, Hongzhuan Chen, Jun Chen
JournalBiomaterials (Biomaterials) Vol. 35 Issue 28 Pg. 8215-26 (Sep 2014) ISSN: 1878-5905 [Electronic] Netherlands
PMID24974009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • APT(EDB) peptide
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Drug Combinations
  • Laminin
  • Peptides
  • Proteoglycans
  • monomethoxypolyethyleneglycol-polylactide block copolymer
  • matrigel
  • Polyethylene Glycols
  • Collagen
  • Paclitaxel
Topics
  • Administration, Intravenous
  • Angiogenesis Inhibitors (chemistry)
  • Animals
  • Antineoplastic Agents (chemistry)
  • Apoptosis
  • Brain Neoplasms (drug therapy)
  • Caveolae (metabolism)
  • Cell Line, Tumor
  • Cell Proliferation
  • Collagen (chemistry)
  • Drug Combinations
  • Endocytosis
  • Female
  • Glioma (drug therapy)
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Laminin (chemistry)
  • Membrane Microdomains (chemistry)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles (chemistry)
  • Neoplasm Transplantation
  • Paclitaxel (chemistry)
  • Particle Size
  • Peptides (chemistry)
  • Polyethylene Glycols (chemistry)
  • Protein Structure, Tertiary
  • Proteoglycans (chemistry)
  • Temperature

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