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- Title
Amphiphilic nanocarrier-induced modulation of PLK1 and miR-34a leads to improved therapeutic response in pancreatic cancer.
- Authors
Gibori, Hadas; Eliyahu, Shay; Krivitsky, Adva; Ben-Shushan, Dikla; Epshtein, Yana; Tiram, Galia; Blau, Rachel; Ofek, Paula; Satchi-Fainaro, Ronit; Ruppin, Eytan; Joo Sang Lee; Landsman, Limor; Golan, Talia; Barshack, Iris; Merquio, Emmanuelle; Blum, Galia
- Abstract
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.
- Subjects
PANCREATIC cancer; ADENOCARCINOMA; SMALL interfering RNA; NANOCARRIERS; MYC oncogenes
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-02283-9