Therapeutic targeting of the mitotic spindle checkpoint through nanoparticle-mediated siRNA delivery inhibits tumor growth in vivo

The mitotic spindle checkpoint is a key signaling pathway that ensures proper chromosome segregation and was suggested as a novel target for anti-cancer treatment. Here, we explore a nanoparticle-based RNAi approach targeting the key spindle checkpoint gene MAD2 to investigate the suitability of the spindle checkpoint as a therapeutic target in vitro and in vivo. Repression of MAD2 causes severe chromosome missegregation in colon carcinoma cells associated with induction of apoptosis. Systemic administration of siRNA nanoparticles in nude mice results in reduced growth of xenograft tumors suggesting that inhibition of the spindle checkpoint represents a promising new concept for cancer therapy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.