title: Superoxide Dismutase 1 Nanozyme for Treatment of Eye Inflammation.
abstract: Use of antioxidants to mitigate oxidative stress during ocular inflammatory diseases has shown therapeutic potential. This work examines a nanoscale therapeutic modality for the eye on the base of antioxidant enzyme, superoxide dismutase 1 (SOD1), termed "nanozyme." The nanozyme is produced by electrostatic coupling of the SOD1 with a cationic block copolymer, poly(L-lysine)-poly(ethyleneglycol), followed by covalent cross-linking of the complexes with 3,3'-dithiobis(sulfosuccinimidylpropionate) sodium salt. The ability of SOD1 nanozyme as well as the native SOD1 to reduce inflammatory processes in the eye was examined in vivo in rabbits with immunogenic uveitis. Results suggested that topical instillations of both enzyme forms demonstrated anti-inflammatory activity; however, the nanozyme was much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as the intensities of corneal and iris edema, hyperemia of conjunctiva, lens opacity, fibrin clots, and the protein content in aqueous humor. Clinical findings were confirmed by histological data. Thus, SOD1-containing nanozyme is potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.
authors.affiliation: Chemistry Faculty, M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Kost
authors.affiliation: Helmholtz Institute for Eye Disease, Moscow 105062, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Beznos
authors.affiliation: Helmholtz Institute for Eye Disease, Moscow 105062, Russia.
authors.forename: Nina G
authors.initials: NG
authors.lastname: Davydova
authors.affiliation: UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7362, USA.
authors.forename: Devika S
authors.initials: DS
authors.lastname: Manickam
authors.affiliation: Chemistry Faculty, M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
authors.forename: Irina I
authors.initials: II
authors.lastname: Nikolskaya
authors.affiliation: Macquarie University, Sydney, NSW 2109, Australia ; Research Institute for Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow 119992, Russia.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Guller
authors.affiliation: Chemistry Faculty, M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
authors.forename: Petr V
authors.initials: PV
authors.lastname: Binevski
authors.affiliation: Helmholtz Institute for Eye Disease, Moscow 105062, Russia.
authors.forename: Natalia B
authors.initials: NB
authors.lastname: Chesnokova
authors.affiliation: Research Institute for Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow 119992, Russia.
authors.forename: Anatoly B
authors.initials: AB
authors.lastname: Shekhter
authors.affiliation: Chemistry Faculty, M.V. Lomonosov Moscow State University, Moscow 119991, Russia ; UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7362, USA ; Pirogov Russian National Research Medical University, Moscow 117997, Russia.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Klyachko
authors.affiliation: Chemistry Faculty, M.V. Lomonosov Moscow State University, Moscow 119991, Russia ; UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7362, USA.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
mesh_terms: D000818:Animals; D003228:Conjunctiva / Q000378:metabolism / Q000473:pathology; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000627:therapeutic use; D013388:Succinimides / Q000737:chemistry; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D000072105:Superoxide Dismutase-1; D014605:Uveitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D011108:Polymers; D011994:Recombinant Proteins; D013388:Succinimides; C035759:3,3'-dithiobis(sulfosuccinimidyl propionate); D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1