RNA interference has tremendous yet unrealized potential to treat a wide range 
of illnesses. Innovative solutions are needed to protect and selectively deliver 
small interfering RNA (siRNA) cargo to and within a target cell to fully exploit 
siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized 
carbon nanotube (fCNT)-mediated transport of siRNA selectively and with high 
efficiency to renal proximal tubule cells in animal models of acute kidney 
injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA 
alone and effectively knocked down the expression of several target genes, 
includingTrp53,Mep1b,Ctr1, andEGFP A clinically relevant cisplatin-induced 
murine model of AKI was used to evaluate the therapeutic potential of 
fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. 
Prophylactic treatment with a combination of fCNT/siMep1band 
fCNT/siTrp53significantly improved progression-free survival compared to 
controls via a mechanism that required concurrent reduction of meprin-1β and p53 
expression. The fCNT/siRNA was well tolerated, and no toxicological consequences 
were observed in murine models. Toward clinical application of this platform, 
fCNTs were evaluated for the first time in nonhuman primates. The rapid and 
kidney-specific pharmacokinetic profile of fCNT in primates was comparable to 
what was observed in mice and suggests that this approach is amenable for use in 
humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means 
for the prevention of AKI to safely overcome the persistent barrier of 
nephrotoxicity during medical intervention.