Journal
BIOMATERIALS
Volume 33, Issue 32, Pages 8167-8176Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.07.046
Keywords
Dual target strategy; Nanoparticles; Brain tumor; Glioma penetration; Anti-glioblastoma; Toxicity
Funding
- National Basic Research Program of China 973 program [2007CB935802]
- National Natural Science Foundation of China [30901862]
- National Science and Technology Major Project [2009ZX09310-006]
- Science and Technology Development Foundation of Nanjing Medical University [2011NJMU271]
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Therapeutic effect of glioma is often limited due to low permeability of delivery systems across the Blood-Brain Barrier (BBB) and poor penetration into the tumor tissue. In order to overcome the two barriers, we proposed Angiopep-conjugated PEG-PCL nanoparticles (ANG-PEG-NP) as a dual targeting drug delivery system for glioma treatment basing on low density lipoprotein receptor related protein (LRP) receptor not only over-expressed on BBB but also on glioma cells. This system could transport across BBB through LRP-mediated transcytosis and then targeted glioma via LRP-mediated endocytosis. In this study, we evaluated the preliminary availability and safety of ANG-PEG-NP for glioma treatment. The penetration, distribution, and accumulation into 3D glioma spheroid and in vivo glioma region of ANG-PEG-NP were obviously higher than that of plain PEG-PCL nanoparticles (PEG-NP). The anti-glioblastoma efficacy of paclitaxel (PTX) loading ANG-PEG-NP was significantly enhanced as compared to that of Taxol and PEG-NP. Preliminary safety results showed that no acute toxicity to hematological system, liver, kidney and brain tissue was observed after intravenous administration with a dose of 100 mg/kg blank ANG-PEG-NP per day for a week. Results indicate that Angiopep-conjugated dual targeting PEG-PCL nanoparticle is a potential brain targeting drug delivery system for glioma treatment. (C) 2012 Elsevier Ltd. All rights reserved.
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