The aim of this work was to explore the use of HA-displaying NPs as an effective strategy to facilitate (i) the targeting of pancreatic cancer cells that are known to express high levels of the HA receptor CD44, (ii) the intracellular delivery of siRNA, and (iii) the knockdown of HIF-1α and its downstream target genes. Here, CD44 is linked to familial pancreatic carcinoma.