Amphiphilic nanocarrier-induced modulation of PLK1 and miR-34a leads to improved therapeutic response in pancreatic cancer

作者：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

来源：Nature Communications, 2018, 9(1): 16.

DOI：10.1038/s41467-017-02283-9

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

• 出版日期2018-1-2
• 单位上海生物信息技术研究中心