Preferential siRNA delivery to injured kidneys for combination treatment of acute kidney injury

Weimin Tang, Yi Chen, Hee Seong Jang, Yu Hang, Chinmay M. Jogdeo, Jing Li, Ling Ding, Chuhan Zhang, Ao Yu, Fei Yu, Kirk W. Foster, Babu J Padanilam, David Oupický

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Acute kidney injury (AKI) is characterized by a sudden loss of renal function and is associated with high morbidity and mortality. Tumor suppressor p53 and chemokine receptor CXCR4 were both implicated in the AKI pathology. Here, we report on the development and evaluation of polymeric CXCR4 antagonist (PCX) siRNA carrier for selective delivery to injured kidneys in AKI. Our results show that PCX/siRNA nanoparticles (polyplexes) provide protection against cisplatin injury to tubule cells in vitro when both CXCR4 and p53 are inhibited. The polyplexes selectively accumulate and are retained in the injured kidneys in cisplatin and bilateral ischemia reperfusion injury models of AKI. Treating AKI with the combined CXCR4 inhibition and p53 gene silencing with the PCX/sip53 polyplexes improves kidney function and decreases renal damage. Overall, our results suggest that the PCX/sip53 polyplexes have a significant potential to enhance renal accumulation in AKI and deliver therapeutic siRNA.

Original languageEnglish (US)
Pages (from-to)300-313
Number of pages14
JournalJournal of Controlled Release
Volume341
DOIs
StatePublished - Jan 2022

Keywords

  • Acute kidney injury
  • CXCR4
  • Polyplexes
  • p53
  • siRNA, nanoparticles

ASJC Scopus subject areas

  • Pharmaceutical Science

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