Effect of disintegrin-loaded chitosan nanoparticles on malignant glioma cells

Abstract

Glioblastoma multiforme (GBM), the most malignant and invasive glioma, accounts for 15% of all brain tumors. The current treatment for GBM involves surgery, radiation and temozolomide chemotherapy. Moreover, recurrent tumors are chemoresistant. Therefore there is a critical need for new and effective therapies for GBM. Recently,investigations have shown that the snake venom disintegrin specifically binds to certain integrins on the surface of glioma cells and thereby inhibits their interaction with the extracellular matrix (ECM), resulting in blockage of cell motility and invasiveness. The targeted therapy with the disintegrin is a promising strategy to block integrins signaling pathway. Despite the beneficial effect of disintegrins, the delivery of protein to brain tumors remains a major problem, mainly due to difficulty penetrating the blood brain barrier. To overcome these problems, we will develop a drug delivery systems which will promote the passage of disintegrin into the brain, thereby blocking integrin signaling pathways resulting in a blockage of cell motility and invasiveness of the glioblastoma. During the research stage at University of Southern California, Los Angeles, under the supervision of the Professor Dr. Florence Hofman, disintegrin-loaded chitosan nanoparticles will be evaluated in vitro using different GBM cell lines, and in vivo in the intracranial GBM xenograft model. (AU)