Polymeric nanoparticles for sustained down-regulation of annexin A2 lead to reduction in proliferation and migration of prostate cancer cells

The annexins represent a large family of Ca²⁺ binding and cellular membrane associated proteins. One member of this protein family annexin A2 has been shown to be over-expressed in a wide variety of cancerous phenotypes. Heterotetrameric cell surface expression of annexin A2 has been shown to be anti-angiogenic and serves as a membrane-bound receptor for angiostatin, tPA and plasminogen, cathepsin-B, and tenascin-C. Loss of regulatory control of annexin A2 in prostate cancer may serve to promote tumor proliferation and metastasis. Here we investigate the use of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles as a potential delivery vehicle for sustained down-regulation of annexin A2. Nanoparticles are loaded with a pDrive-sh plasmid DNA construct producing a 20 base siRNA that inhibits annexin A2 transcription. Upon exposure of pDrive-sh loaded nanoparticles to DU-145 and PC-3 metastatic prostate cancer cells we observe sustained changes in cellular proliferation. Significant inhibition in the migratory ability of these cells is also evident. Our results indicate that nanoparticle mediated induced down-regulation of annexin A2 may serve as a future therapeutic strategy for the treatment of prostate cancers.