Superoxide Dismutase 1 Nanozyme for Treatment of Eye Inflammation

Author:

Kost Olga A.1,Beznos Olga V.2,Davydova Nina G.2,Manickam Devika S.3,Nikolskaya Irina I.1,Guller Anna E.45,Binevski Petr V.1,Chesnokova Natalia B.2,Shekhter Anatoly B.5,Klyachko Natalia L.136,Kabanov Alexander V.13

Affiliation:

1. Chemistry Faculty, M.V. Lomonosov Moscow State University, Moscow 119991, Russia

2. Helmholtz Institute for Eye Disease, Moscow 105062, Russia

3. UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7362, USA

4. Macquarie University, Sydney, NSW 2109, Australia

5. Research Institute for Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow 119992, Russia

6. Pirogov Russian National Research Medical University, Moscow 117997, Russia

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 examinedin vivoin 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.

Funder

National Institutes of Health

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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