title: Gracilaria lemaneiformis polysaccharide as integrin-targeting surface decorator of selenium nanoparticles to achieve enhanced anticancer efficacy.
abstract: 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 αvβ3 integrin overexpressed in glioma cells, was employed in the present study to functionalize selenium nanoparticles (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 cyclo-(Arg-Gly-Asp-Phe-Lys) peptides, suggesting that cellular uptake into U87 cells and C6 cells occurred via αvβ3 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.
authors: Department of Chemistry and ‡Institute of Hydrobiology, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
authors: Wenting
authors: W
authors: Jiang
authors: Yuanting
authors: Y
authors: Fu
authors: Fang
authors: F
authors: Yang
authors: Yufeng
authors: Y
authors: Yang
authors: Ting
authors: T
authors: Liu
authors: Wenjie
authors: W
authors: Zheng
authors: Lilan
authors: L
authors: Zeng
authors: Tianfeng
authors: T
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D044724:Gracilaria / Q000737:chemistry*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D042541:Intracellular Space / Q000737:chemistry; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D016023:Integrins; D010455:Peptides; D011134:Polysaccharides; D017382:Reactive Oxygen Species; D020169:Caspases; D012643:Selenium