Exosome-mediated delivery of superoxide dismutase for anti-aging studies in Caenorhabditis elegans

Int J Pharm. 2023 Jun 25:641:123090. doi: 10.1016/j.ijpharm.2023.123090. Epub 2023 Jun 1.

Abstract

Aging is a dynamic and progressive process mediated by reactive oxygen species (ROS), and the antioxidant enzyme superoxide dismutase (SOD) can effectively scavenge ROS to extend longevity. However, the instability and impermeability of native enzyme limit its in vivo biomedical application. Currently, exosome as protein carriers attracts considerable attention in the disease treatment owing to low immunogenicity and high stability. Herein, SOD was encapsulated into exosomes via mechanical extrusion with saponin permeabilization to obtain SOD-loaded EXO (SOD@EXO). SOD@EXO with a hydrodynamic diameter of 101.7 ± 5.6 nm could scavenge excessive ROS and protect the cells from oxidative damage induced by 1-methyl-4-phenylpyridine. Compared with native SOD, SOD@EXO significantly extended the lifespan of N2 wild-type Caenorhabditis elegans under normal conditions. Moreover, SOD@EXO improved the resistance against heat and oxidative stress, leading to notable survival ratio under these hostile conditions. Overall, the exosome-mediated delivery of SOD could reduce ROS level and delay aging in C. elegans model, thereby providing potential strategies to treat ROS-related diseases in future.

Keywords: Anti-aging; Exosome; Reactive oxygen species; Superoxide dismutase.

MeSH terms

  • Aging / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans Proteins* / pharmacology
  • Exosomes* / metabolism
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase / pharmacology

Substances

  • Reactive Oxygen Species
  • Caenorhabditis elegans Proteins
  • Superoxide Dismutase
  • Antioxidants