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Gibori, Hadas; Eliyahu, Shay; Krivitsky, Adva; Ben-Shushan, Dikla; Epshtein, Yana; Tiram, Galia; Blau, Rachel; Ofek, Paula; Lee, Joo Sang; Ruppin, Eytan; Landsman, Limor; Barshack, Iris; Golan, Talia; Merquiol, Emmanuelle; Blum, Galia; Satchi-Fainaro, Ronit
Nature communications, 01/2018, Letnik: 9, Številka: 1Journal Article
The heterogeneity of pancreatic ductal adenocarcinoma (PDAC) suggests that successful treatment might rely on simultaneous targeting of multiple genes, which can be achieved by RNA interference-based therapeutic strategies. Here we show a potent combination of microRNA and siRNA delivered by an efficient nanocarrier to PDAC tumors. Using proteomic-microRNA profiles and survival data of PDAC patients from TCGA, we found a novel signature for prolonged survival. Accordingly, we used a microRNA-mimic to increase miR-34a together with siRNA to silence PLK1 oncogene. For in vivo dual-targeting of this combination, we developed a biodegradable amphiphilic polyglutamate amine polymeric nanocarrier (APA). APA-miRNA-siRNA polyplexes systemically administered to orthotopically inoculated PDAC-bearing mice showed no toxicity and accumulated at the tumor, resulting in an enhanced antitumor effect due to inhibition of MYC oncogene, a common target of both miR-34a and PLK1. Taken together, our findings warrant this unique combined polyplex's potential as a novel nanotherapeutic for PDAC.
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in: SICRIS
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