509728 Ammonium-Functionalized Carbon Nanotubes for Nucleic Acid Delivery in a Hypoxia-Induced Model of Acute Kidney Injury

Michael Lange1,2, Aleksandra M. Urbanska1, Bryan Aristega Almeida1, Sam Wong1,3, David A. Scheinberg1 and Michael R. McDevitt1, (1)Memorial Sloan Kettering Cancer Center, New York, NY, (2)The Cooper Union for the Advancement of Science and Art, New York, NY, (3)Hunter College, New York, NY

Acute kidney injury (AKI) is a detrimental side effect of pharmaceutical treatment, particularly chemotherapy, and abdominal surgery. Ammonium-functionalized carbon nanotubes (fCNT) are a renal small interfering RNA (siRNA) delivery platform that have been used to prevent cisplatin-induced AKI in mice. To explore other causes of AKI, a precision-cut hypoxia-induced murine model of AKI is described here. RNA interference (RNAi) therapy using siRNA against Trp53 and Mep1b, two genes responsible for AKI progression, bound to fCNT (fCNT/siTrp53/Mep1b) decreases renal expression of pro-inflammatory cytokines in prophylactically treated mice. A robust hypoxia-induced model of AKI is developed and used to probe transcriptome changes and the therapeutic effect of fCNT/siTrp53/Mep1b.

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