title: Hyaluronic acid oligosaccharide modified redox-responsive mesoporous silica nanoparticles for targeted drug delivery.
abstract: A redox-responsive delivery system based on colloidal mesoporous silica (CMS) has been developed, in which 6-mercaptopurine (6-MP) was conjugated to vehicles by cleavable disulfide bonds. The oligosaccharide of hyaluronic acid (oHA) was modified on the surface of CMS by disulfide bonds as a targeting ligand and was able to increase the stability and biocompatibility of CMS under physiological conditions. In vitro release studies indicated that the cumulative release of 6-MP was less than 3% in the absence of glutathione (GSH), and reached nearly 80% within 2 h in the presence of 3 mM GSH. Confocal microscopy and fluorescence-activated cell sorter (FACS) methods were used to evaluate the cellular uptake performance of fluorescein isothiocyanate (FITC) labeled CMS, with and without oHA modification. The CMS-SS-oHA exhibited a higher cellular uptake performance via CD44 receptor-mediated endocytosis in HCT-116 (CD44 receptor-positive) cells than in NIH-3T3 (CD44 receptor-negative) cells. 6-MP loaded CMS-SS-oHA exhibited greater cytotoxicity against HCT-116 cells than NIH-3T3 cells due to the enhanced cell uptake behavior of CMS-SS-oHA. This study provides a novel strategy to covalently link bioactive drug and targeting ligand to the interiors and exteriors of mesoporous silica to construct a stimulus-responsive targeted drug delivery system.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , 103 Wenhua Road, Shenyang 110016, People's Republic of China.
authors.forename: Qinfu
authors.initials: Q
authors.lastname: Zhao
authors.forename: Hongjian
authors.initials: H
authors.lastname: Geng
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yikun
authors.initials: Y
authors.lastname: Gao
authors.forename: Jiahao
authors.initials: J
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinghai
authors.initials: J
authors.lastname: Zhang
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D045325:HCT116 Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry; D015122:Mercaptopurine / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009844:Oligosaccharides / Q000737:chemistry*; D010084:Oxidation-Reduction; D016062:Porosity; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D009844:Oligosaccharides; D012710:Serum Albumin, Bovine; D012822:Silicon Dioxide; D006820:Hyaluronic Acid; D015122:Mercaptopurine; D005978:Glutathione
keywords: 6-mercaptopurine; CD44 receptors; colloidal mesoporous silica; oligosaccharide of hyaluronic acid; redox-responsive