Glyco-Nanoparticles with Sheddable Saccharide Shells: A Unique and Potent Platform for Hepatoma-Targeting Delivery of Anticancer Drugs

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• 作者：Wei Chen ; Yan Zou ; Fenghua Meng ; Ru Cheng ; Chao Deng ; Jan Feijen ; Zhiyuan Zhong
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：March 10, 2014
• 年：2014
• 卷：15
• 期：3
• 页码：900-907
• 全文大小：496K
• 年卷期：v.15,no.3(March 10, 2014)
• ISSN：1526-4602

文摘

Reduction-sensitive shell-sheddable glyco-nanoparticles were designed and developed based on poly(蔚-caprolactone)-graft-SS-lactobionic acid (PCL-g-SS-LBA) copolymer for efficient hepatoma-targeting delivery of doxorubicin (DOX). PCL-g-SS-LBA was prepared by ring-opening copolymerization of 蔚-caprolactone and pyridyl disulfide carbonate followed by postpolymerization modification with thiolated lactobionic acid (LBA-SH) via thiol-disulfide exchange reaction. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that PCL-g-SS-LBA was self-assembled into monodisperse nanoparticles (SS-GNs) with a mean diameter of about 80 nm. SS-GNs while remaining stable under physiological conditions (37 掳C, pH 7.4) were prone to rapid shell-shedding and aggregation in the presence of 10 mM dithiothreitol (DTT). DOX was loaded into SS-GNs with a decent loading content of 12.0 wt %. Notably, in vitro release studies revealed that about 80.3% DOX was released from DOX-loaded SS-GNs in 24 h under a reductive condition while low drug release (<21%) was observed for DOX-loaded PCL-g-LBA nanoparticles (reduction-insensitive control) under otherwise the same condition and for DOX-loaded SS-GNs under a nonreductive condition. The flow cytometry and confocal microscopy observations indicated that SS-GNs were efficiently taken up by asialoglycoprotein receptor (ASGP-R)-overexpressing HepG2 cells likely via a receptor-mediated endocytosis mechanism and DOX was released into the nuclei of cells following 4 h incubation. MTT assays showed that DOX-loaded SS-GNs exhibited a high antitumor activity toward HepG2 cells, which was comparable to free DOX and about 18-fold higher than their reduction-insensitive counterparts, while blank SS-GNs were nontoxic up to a tested concentration of 1.0 mg/mL. These shell-sheddable glyco-nanoparticles are promising for hepatoma-targeting chemotherapy.