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Synergistic targeting tenascin C and neuropilin-1 for specific penetration of nanoparticles for anti-glioblastoma treatment

Paper ID Volume ID Publish Year Pages File Format Full-Text
5337 367 2016 16 PDF Available
Title
Synergistic targeting tenascin C and neuropilin-1 for specific penetration of nanoparticles for anti-glioblastoma treatment
Abstract

The pathological and physiological barriers of glioblastoma multiforme (GBM) lead to insufficient extravasation and penetration of nano-sized therapeutics. As the main driver of interstitial fluid pressure-related drug efflux, the aberrant extracellular matrix (ECM) appears to be a valuable target that plays a crucial role in forming pathological barriers of GBM. Herein, a new Ft peptide was synthesized by coupling FHK and tLyp-1 sequence together via a cysteine to synergistically target glioma-associated tenascin C (extracellular matrix component) and neuropilin-1 on neovasculature and glioma cells to enable specific penetration of nanoparticles for anti-glioblastoma treatment. In vitro, Ft peptide-functionalization not only enabled the internalization of poly (ethyleneglycol)-poly (lactic acid) nanoparticulate system in 2D U87 MG cells and HUVEC cells but also facilitated its deep penetration in 3D glioma spheroids. Similarly, in vivo real-time 2D and 3D imaging clearly showed a substantial accumulation of the Ft-functionalized nanoparticles (Ft-NP) in the glioma foci of intracranial U87 glioma-bearing mice. Glioma distribution assay demonstrated a tenascin C-mediated accumulation in glioma foci and neuropilin-1-mediated transportation through glioma cells. Paclitaxel-loaded Ft-NP (Ft-NP-PTX) induced higher cytotoxic effect and apoptosis rate compared with FHK or tLyp-1-modified ones. The highest anti-glioma efficacy was also achieved following the i.v. administration of Ft-NP-PTX, with a median survival promotion of 269% than that of the saline-treated mice, while only limited life span promotion was obtained after the treatment of other formulations (31.3%, 59.4%, 134.4% and 109.3% respectively for Taxol®, NP-PTX, tLyp-1-NP-PTX and FHK-NP-PTX). In conclusion, all these evidences together verified the improved therapeutic effect of Ft-NP-PTX for anti-glioma drug delivery via neuropilin-1- and tenascin C-mediated specific penetration of nanoparticles in to glioma parenchyma.

Keywords
Glioma therapy; Drug delivery; Penetration; Synergistic effect; Extracellular matrix
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 101, September 2016, Pages 60–75
Authors
, , , , , , , , , , , ,
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