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PEG-co-PCL nanoparticles modified with MMP-2/9 activatable low molecular weight protamine for enhanced targeted glioblastoma therapy

Paper ID Volume ID Publish Year Pages File Format Full-Text
6749 514 2013 13 PDF Available
Title
PEG-co-PCL nanoparticles modified with MMP-2/9 activatable low molecular weight protamine for enhanced targeted glioblastoma therapy
Abstract

By taking advantage of the dramatically upregulated expression of matrix metalloproteinases MMP-2 and MMP-9 in glioblastomas and the powerful transport ability of low molecular weight protamine (LMWP), we constructed an activatable low molecular weight protamine (ALMWP) and conjugated it to PEG-PCL nanoparticles (NP) to develop a ‘smart’ drug delivery system for enhanced targeted glioblastoma therapy. Important parameters such as particle size distribution, zeta potential and surface content were determined, which confirmed the conjugation of ALMWP to the surface of nanoparticle. ALMWP-NP loaded with paclitaxel (PTX) exhibited a desirable pharmacokinetic and biodistribution profiles for anti-glioblastoma drug delivery. Cellular experiments showed that ALMWP-NP exhibited significantly elevated MMP-dependent cellular accumulation in C6 cells via lipid raft-mediated endocytosis and energy-dependent macropinocytosis, and improved the cytotoxicity of PTX. In vitro C6 tumor spheroid uptake confirmed the tumor penetrating ability of ALMWP-NP, in vivo imaging and glioma distribution justified its specific accumulation in the glioma. The improved glioma-targeting and tumor penetration led to an anticipated enhanced in vivo anti-glioblastoma effect: animals (nude mice bearing intracranial C6 glioma) treated with ALMWP-NP-PTX survive significantly longer than those treated with saline, Taxol® NP-PTX and LMWP-NP-PTX. The findings here offered strong evidence for the glioblastoma-targeting therapy of ALMWP-NP-PTX, and could also lead to a significant advancement in the application of CPPs for targeted therapy of glioma.

Keywords
Activatable cell penetrating peptide; Nanoparticle; Chemotherapy; Paclitaxel; Drug delivery system; Anti-glioblastoma
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PEG-co-PCL nanoparticles modified with MMP-2/9 activatable low molecular weight protamine for enhanced targeted glioblastoma therapy
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 1, January 2013, Pages 196–208
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us