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Co-administration of Dual-Targeting Nanoparticles with Penetration Enhancement Peptide for Antiglioblastoma Therapy
journal contribution
posted on 2014-01-06, 00:00 authored by Deyu Miao, Mengyin Jiang, Zhongyang Liu, Guangzhi Gu, Quanyin Hu, Ting Kang, Qingxiang Song, Lei Yao, Wei Li, Xiaoling Gao, Mingjiang Sun, Jun ChenChemotherapy
is an indispensable auxiliary treatment for glioma
but highly limited by the existence of both blood–brain barrier
(BBB) and blood–brain tumor barrier (BBTB). The dysfunctional
brain tumor blood vessels and high interstitial pressure in glioma
also greatly hindered the accumulation and deep penetration of chemotherapeutics
into the glioma. Lactoferrin (Lf), with its receptor overexpressed
on both the brain endothelial cells and glioma cells, was here functionalized
to the surface of poly(ethylene glycol)–poly(lactic acid) nanoparticles
to mediate BBB/BBTB and glioma cell dual targeting. tLyP-1, a tumor-homing
peptide, which contains a C-end Rule sequence that can mediate tissue
penetration through the neuropilin-1-dependent internalization pathway,
was coadministrated with Lf-functionalized nanoparticles (Lf-NP) to
enhance its accumulation and deep penetration into the glioma parenchyma.
Enhanced cellular association in both BCEC and C6 cells, increased
cytotoxicity of the loaded paclitaxel, and deep penetration in the
3D glioma spheroids was achieved by Lf-NP. Following coadministration
with tLyP-1, the functionalized nanoparticles obtained improved tumor
targeting, glioma vascular extravasation, and antiglioma efficacy.
The findings here suggested that the strategy by coadministrating
BBB/BBTB and glioma cells dual-targeting nanocarriers with a tumor
penetration enhancement peptide represent a promising platform for
antiglioma drug delivery.
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3 D glioma spheroidsfunctionalized nanoparticlesBBTBantiglioma drug deliverytumor penetration enhancement peptideglioma cellreceptor overexpressedAntiglioblastoma TherapyChemotherapyC 6 cellsglioma cellsglioma parenchymaBBBantiglioma efficacyPenetration Enhancement PeptideBCECdysfunctional brain tumor blood vesselstissue penetration
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