Polymer/Nanoceria Hybrid Polyplexes for Gene and Antioxidant Delivery

Landon Mott, Matthew Hancock, Eric A. Grulke, Daniel W. Pack

Research output: Contribution to journalArticlepeer-review


Various diseases, including cancers and inflammatory diseases, are characterized by a disruption of redox homeostasis, suggesting the need for synergistic treatments involving co-delivery of gene therapies and free radical scavengers. In this report, polyethylenimine (PEI), nanoceria (NC), and DNA were complexed to form nanoparticles providing simultaneous delivery of a gene and an antioxidant. NC was coated in citric acid to provide stable, 4 nm particles that electrostatically bound PEI/DNA polyplexes. The resulting ternary particles transfected HeLa cells with similar efficiency to that of ternary polyplexes comprising 15 kDa poly-l-α-glutamic acid/PEI/DNA while providing smaller particle sizes by more than 100 nm. NC/PEI/DNA polyplexes exhibited enhanced radical-scavenging activity compared to free NC, and oxidative stress from the superoxide-generating agent, menadione, could be completely reversed by the delivery of NC/PEI/DNA polyplexes. Transfection by NC/PEI/DNA polyplexes was demonstrated to occur efficiently through caveolin-mediated endocytosis and macropinocytosis. Co-delivery of genes encoding reactive oxygen species-scavenging proteins, transcription factors, growth factors, tumor suppressors, or anti-inflammatory genes with NC, therefore, may be a promising strategy in synergistic therapeutics.

Original languageEnglish
Pages (from-to)3166-3175
Number of pages10
JournalACS Applied Bio Materials
Issue number8
StatePublished - Aug 21 2023

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society


  • antioxidant
  • gene delivery
  • hybrid polyplex
  • nanoceria
  • polyethylenimine

ASJC Scopus subject areas

  • Biomaterials
  • General Chemistry
  • Biomedical Engineering
  • Biochemistry, medical


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