Kidney-targeted redox scavenger therapy prevents cisplatin-induced acute kidney injury Journal Article

Authors: Williams, R. M.; Shah, J.; Mercer, E.; Tian, H. S.; Thompson, V.; Cheung, J. M.; Dorso, M.; Kubala, J. M.; Gudas, L. J.; de Stanchina, E.; Jaimes, E. A.; Heller, D. A.
Article Title: Kidney-targeted redox scavenger therapy prevents cisplatin-induced acute kidney injury
Abstract: Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. We investigated a drug delivery strategy to improve the pharmacokinetics of an approved therapy that does not normally demonstrate appreciable efficacy in CI-AKI, as a preventive intervention. In prior work, we developed a kidney-selective mesoscale nanoparticle (MNP) that targets the renal proximal tubular epithelium. Here, we found that the nanoparticles target the kidneys in a mouse model of CI-AKI with significant damage. We evaluated MNPs loaded with the reactive oxygen species scavenger edaravone, currently used to treat stroke and ALS. We found a marked and significant therapeutic benefit with edaravone-loaded MNPs, including improved renal function, which we demonstrated was likely due to a decrease in tubular epithelial cell damage and death imparted by the specific delivery of edaravone. The results suggest that renal-selective edaravone delivery holds potential for the prevention of acute kidney injury among patients undergoing cisplatin-based chemotherapy. Copyright © 2022 Williams, Shah, Mercer, Tian, Thompson, Cheung, Dorso, Kubala, Gudas, de Stanchina, Jaimes and Heller.
Keywords: cisplatin; nanomedicine; pharmacology; acute kidney injury; drug repurposing; redox scavenger
Journal Title: Frontiers in Pharmacology
Volume: 12
ISSN: 1663-9812
Publisher: Frontiers Media S.A.  
Date Published: 2022-01-03
Start Page: 790913
Language: English
DOI: 10.3389/fphar.2021.790913
PROVIDER: scopus
PMCID: PMC8762298
PUBMED: 35046813
Notes: Article -- Export Date: 1 February 2022 -- Source: Scopus
Citation Impact
MSK Authors
  1. Daniel Alan Heller
    87 Heller
  2. Janki Kalpesh Shah
    21 Shah
  3. Edgar Alberto Jaimes
    56 Jaimes
  4. Helen Tian
    4 Tian
  5. Madeline Anne Dorso
    4 Dorso
  6. Justin M Cheung
    4 Cheung
  7. Elizabeth Mercer
    1 Mercer
  8. Jaclyn Marie Kubala
    1 Kubala