Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 6, Issue 16, Pages 13738-13748Publisher
AMER CHEMICAL SOC
DOI: 10.1021/am5031962
Keywords
cancer targeting; glioblastoma; selenium nanoparticles; polysaccharide; apoptosis
Funding
- National High Technology Research and Development Program of China (863 Program) [SS2014AA020538]
- Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province
- Science Foundation for Distinguished Young Scholars of Guangdong Province
- Program for New Century Excellent Talents in University
- Yang Fan Innovative & Entrepreneurial Research Team Project
- Research Fund for the Doctoral Program of Higher Education of China
- China Postdoctoral Science Foundation
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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 (alpha(V)beta(3) integrin overexpressed in glioma cells, was employed in the present study to functionalize selenium nanopartides (SeNPs) to achieve antiglioblastoma efficacy. GLP-SeNPs 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-SeNPs exhibited significantly higher cellular uptake than unmodified SeNPs. As expected, U87 cells exhibited a greater uptake of GLP-SeNPs than C6 cells with low integrin expression level. Furthermore, the internalization of GLP-SeNPs was inhibited by and C6 cells occurred via alpha(v)beta(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 SeNPs 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.
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