SOD1 nanozyme with reduced toxicity and MPS accumulation

Yuhang Jiang, Phonepasong Arounleut, Steven Rheiner, Younsoo Bae, Alexander V. Kabanov, Carol Milligan, Devika S. Manickam

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

We previously developed a "cage"-like nano-formulation (nanozyme) for copper/Zinc superoxide dismutase (SOD1) by polyion condensation with a conventional block copolymer poly(ethylene glycol)-b-poly(L-lysine) (PEG-PLL) followed by chemical cross-linking. Herein we report a new SOD1 nanozyme based on PEG-b-poly(aspartate diethyltriamine) (PEG-PAsp(DET), or PEG-DET for short) engineered for chronic dosing. This new nanozyme was spherical (Rg/Rh = 0.785), and hollow (60% water composition) nanoparticles with colloidal properties similar to PLL-based nanozyme. It was better tolerated by brain microvessel endothelial/neuronal cells, and accumulated less in the liver and spleen. This formulation reduced the infarct volumes by more than 50% in a mouse model of ischemic stroke. However, it was not effective at preventing neuromuscular junction denervation in a mutant SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS). To our knowledge, this work is the first report of using PEG-DET for protein delivery and a direct comparison between two cationic block copolymers demonstrating the effect of polymer structure in modulating the mononuclear phagocyte system (MPS) accumulation of polyion complexes.

Original languageEnglish
Pages (from-to)38-49
Number of pages12
JournalJournal of Controlled Release
Volume231
DOIs
StatePublished - Jun 10 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.

Keywords

  • ALS
  • Antioxidant
  • MPS
  • Mouse
  • PEG-PAsp(DET)
  • PEG-PLL
  • Protein delivery
  • Stroke
  • Superoxide dismutase
  • Toxicity

ASJC Scopus subject areas

  • Pharmaceutical Science

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