Gracilaria lemaneiformis Polysaccharide as Integrin-Targeting Surface Decorator of Selenium Nanoparticles to Achieve Enhanced Anticancer Efficacy

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• 作者：Wenting Jiang ; Yuanting Fu ; Fang Yang ; Yufeng Yang ; Ting Liu ; Wenjie Zheng ; Lilan Zeng ; Tianfeng Chen
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2014
• 出版时间：August 27, 2014
• 年：2014
• 卷：6
• 期：16
• 页码：13738-13748
• 全文大小：558K
• ISSN：1944-8252

文摘

The poor permeability of glioma parenchyma represents a major limit for antiglioblastoma drug delivery. Gracilaria lemaneiformis polysaccharide (GLP), which has a high binding affinity to 伪_v尾₃ integrin overexpressed in glioma cells, was employed in the present study to functionalize selenium nanoparticles (SeNPs) to achieve antiglioblastoma efficacy. GLP鈥揝eNPs showed satisfactory size distribution, high stability, and selectivity between cancer and normal cells. In U87 glioma cell membrane, which has a high integrin expression level, GLP鈥揝eNPs exhibited significantly higher cellular uptake than unmodified SeNPs. As expected, U87 cells exhibited a greater uptake of GLP鈥揝eNPs than C6 cells with low integrin expression level. Furthermore, the internalization of GLP鈥揝eNPs was inhibited by cyclo-(Arg-Gly-Asp-Phe-Lys) peptides, suggesting that cellular uptake into U87 cells and C6 cells occurred via 伪_v尾₃ integrin-mediated endocytosis. For U87 cells, the cytotoxicity of SeNPs decorated by GLP was enhanced significantly because of the induction of various apoptosis signaling pathways. Internalized GLP鈥揝eNPs triggered intracellular reactive oxygen species downregulation. Therefore, p53, MAPKs, and AKT pathways were activated to advance cell apoptosis. These findings suggest that surface decoration of nanomaterials with GLP could be an efficient strategy for design and preparation of glioblastoma targeting nanodrugs.

Keywords:

cancer targeting; glioblastoma; selenium nanoparticles; polysaccharide; apoptosis