Amphiphilic nanocarrier leads to improved therapeutic response in pancreatic cancer

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. Hadas Gibori (Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University) and his team show here 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, they found a novel signature for prolonged survival. Accordingly, they used a microRNA-mimic to increase miR-34a together with siRNA to silence PLK1 oncogene. For in vivo dual-targeting of this combination, they 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, their findings warrant this unique combined polyplex’s potential as a novel nanotherapeutic for PDAC.

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