title: Approach To Deliver Two Antioxidant Enzymes with Mesoporous Silica Nanoparticles into Cells.
abstract: Reactive oxygen species (ROS) are important factors in many clinical diseases. However, direct delivery of antioxidant enzymes into cells is difficult due to poor cell uptake. A proper design of delivery of enzymes by nanoparticles is very desirable for therapeutic purposes. To overcome the cell barrier problem, a designed mesoporous silica nanoparticle (MSN) system with attached TAT-fusion denatured enzyme for enhancing cell membrane penetration has been developed. Simultaneous delivery of two up-downstream antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase(GPx), reveals synergistic efficiency of ROS scavenging, compared to single antioxidant enzyme delivery. TAT peptide conjugation provided a facile nonendocytosis cell uptake and escape from endosome while moving and aggregating along the cytoskeleton that would allow them to be close to each other at the same time, resulting in the cellular antioxidation cascade reaction. The two-enzyme delivery shows a significant synergistic effect for protecting cells against ROS-induced cell damage and cell cycle arrest. The nanocarrier strategy for enzyme delivery demonstrates that intracellular anti-ROS cascade reactions could be regulated by multifunctional MSNs carrying image fluorophore and relevant antioxidation enzymes.
authors.affiliation: Department of Chemistry, National Taiwan University , Taipei 106, Taiwan.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lin
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Mackay Junior College of Medicine , Nursing and Management, Taipei 112, Taiwan.|Department of Surgery, Mackay Memorial Hospital , Taipei 104, Taiwan.
authors.forename: Tsang-Pai
authors.initials: TP
authors.lastname: Liu
authors.affiliation: Department of Optics and Photonics, National Central University , Taoyuan City 320, Taiwan.
authors.forename: Fan-Ching
authors.initials: FC
authors.lastname: Chien
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Chou
authors.forename: Chien-Tsu
authors.initials: CT
authors.lastname: Chen
authors.affiliation: Department of Chemistry, National Taiwan University , Taipei 106, Taiwan.
authors.forename: Chung-Yuan
authors.initials: CY
authors.lastname: Mou
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry; D005979:Glutathione Peroxidase / Q000008:administration & dosage* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry; D011489:Protein Denaturation; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000737:chemistry; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000737:chemistry; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000975:Antioxidants; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D012822:Silicon Dioxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: antioxidant enzyme; cascade reaction; codelivery; glutathione peroxidase; mesoporous silica nanoparticle; reactive oxygen species; superoxide dismutase