Cross-linked antioxidant nanozymes for improved delivery to CNS

Natalia L. Klyachko, Devika S. Manickam, Anna M. Brynskikh, Svetlana V. Uglanova, Shu Li, Sheila M. Higginbotham, Tatiana K Bronich, Elena V. Batrakova, Alexander V. Kabanov

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Formulations of antioxidant enzymes, superoxide dismutase 1 (SOD1, also known as Cu/Zn SOD) and catalase were prepared by electrostatic coupling of enzymes with cationic block copolymers, polyethyleneimine-poly(ethylene glycol) or poly(L-lysine)-poly(ethylene glycol), followed by covalent cross-linking to stabilize nanoparticles (NPs). Different cross-linking strategies (using glutaraldehyde, bis-(sulfosuccinimidyl)suberate sodium salt or 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride with N-hydroxysulfosuccinimide) and reaction conditions (pH and polycation/protein charge ratio) were investigated that allowed immobilizing active enzymes in cross-linked NPs, termed "nanozymes." Bienzyme NPs, containing both SOD1 and catalase were also formulated. Formation of complexes was confirmed using denaturing gel electrophoresis and western blotting; physicochemical characterization was conducted using dynamic light scattering and atomic force microscopy. In vivo studies of 125I-labeled SOD1-containing nanozymes in mice demonstrated their increased stability in both blood and brain and increased accumulation in brain tissues, in comparison with non-cross-linked complexes and native SOD1. Future studies will evaluate the potential of these formulations for delivery of antioxidant enzymes to the central nervous system to attenuate oxidative stress associated with neurological diseases. From the Clinical Editor: Formulations of antioxidant enzyme complexes were demonstrated along with their increased stability in both blood and brain and increased accumulation in CNS tissue. Future studies will evaluate the potential of these formulations for antioxidant enzyme deliver to the CNS to attenuate oxidative stress in neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Antioxidants
Enzymes
Nanoparticles
Brain
Oxidative stress
Catalase
Polyethylene glycols
Oxidative Stress
Blood
Ethyldimethylaminopropyl Carbodiimide
Neurodegenerative diseases
Tissue
Polyethyleneimine
Ethylene Glycol
Atomic Force Microscopy
Neurology
Glutaral
Dynamic light scattering
Electrophoresis
Static Electricity

Keywords

  • Brain delivery
  • Cross-linking
  • Nanozymes
  • Polyion complexes

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Cite this

Klyachko, N. L., Manickam, D. S., Brynskikh, A. M., Uglanova, S. V., Li, S., Higginbotham, S. M., ... Kabanov, A. V. (2012). Cross-linked antioxidant nanozymes for improved delivery to CNS. Nanomedicine: Nanotechnology, Biology, and Medicine, 8(1), 119-129. https://doi.org/10.1016/j.nano.2011.05.010

Cross-linked antioxidant nanozymes for improved delivery to CNS. / Klyachko, Natalia L.; Manickam, Devika S.; Brynskikh, Anna M.; Uglanova, Svetlana V.; Li, Shu; Higginbotham, Sheila M.; Bronich, Tatiana K; Batrakova, Elena V.; Kabanov, Alexander V.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 8, No. 1, 01.01.2012, p. 119-129.

Research output: Contribution to journalArticle

Klyachko, NL, Manickam, DS, Brynskikh, AM, Uglanova, SV, Li, S, Higginbotham, SM, Bronich, TK, Batrakova, EV & Kabanov, AV 2012, 'Cross-linked antioxidant nanozymes for improved delivery to CNS', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 8, no. 1, pp. 119-129. https://doi.org/10.1016/j.nano.2011.05.010
Klyachko NL, Manickam DS, Brynskikh AM, Uglanova SV, Li S, Higginbotham SM et al. Cross-linked antioxidant nanozymes for improved delivery to CNS. Nanomedicine: Nanotechnology, Biology, and Medicine. 2012 Jan 1;8(1):119-129. https://doi.org/10.1016/j.nano.2011.05.010
Klyachko, Natalia L. ; Manickam, Devika S. ; Brynskikh, Anna M. ; Uglanova, Svetlana V. ; Li, Shu ; Higginbotham, Sheila M. ; Bronich, Tatiana K ; Batrakova, Elena V. ; Kabanov, Alexander V. / Cross-linked antioxidant nanozymes for improved delivery to CNS. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2012 ; Vol. 8, No. 1. pp. 119-129.
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