title: Intracellular antioxidants dissolve man-made antioxidant nanoparticles: using redox vulnerability of nanoceria to develop a responsive drug delivery system.
abstract: Regeneratable antioxidant property of nanoceria has widely been explored to minimize the deleterious influences of reactive oxygen species. Limited information is, however, available regarding the biological interactions and subsequent fate of nanoceria in body fluids. This study demonstrates a surprising dissolution of stable and ultrasmall (4 nm) cerium oxide nanoparticles (CeO2 NPs) in response to biologically prevalent antioxidant molecules (glutathione, vitamin C). Such a redox sensitive behavior of CeO2 NPs is subsequently exploited to design a redox responsive drug delivery system for transporting anticancer drug (camptothecin). Upon exposing the CeO2 capped and drug loaded nanoconstruct to vitamin c or glutathione, dissolution-accompanied aggregation of CeO2 nanolids unleashes the drug molecules from porous silica to achieve a significant anticancer activity. Besides stimuli responsive drug delivery, immobilization of nanoceria onto the surface of mesoporous silica also facilitates us to gain a basic insight into the biotransformation of CeO2 in physiological mediums.
authors.affiliation: State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, ‡College of Life Science, Jilin University , Changchun 130012, P. R. China.
authors.forename: Faheem
authors.initials: F
authors.lastname: Muhammad
authors.forename: Aifei
authors.initials: A
authors.lastname: Wang
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Qi
authors.forename: Shixing
authors.initials: S
authors.lastname: Zhang
authors.forename: Guangshan
authors.initials: G
authors.lastname: Zhu
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D002166:Camptothecin / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002563:Cerium / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D002563:Cerium; C030583:ceric oxide; D012822:Silicon Dioxide; D002166:Camptothecin
keywords: antioxidants; chemotherapy; controlled release; nanoceria; reactive oxygen species; redox responsive